NexGard Plus vs Simparica Trio - Which Is the Best Parasite Preventative for Dogs?

Are all-in-one parasite preventatives the best option for your dog’s long-term health? 

As more pet parents search for simplified yet effective ways to protect their dogs from fleas, ticks, heartworms, and intestinal worms, two most prominent contenders — Simparica Trio and NexGard Plus — have quickly become the go-to choices among veterinarians and dog owners alike.

NexGard Plus and Simparica Trio are prescription chewables that combine active ingredients to protect against multiple parasites. Their similar profiles can blur key differences.

In a study comparing their performance against a macrocyclic lactone-resistant isolate (JYD-34) of Dirofilaria immitis (the parasite responsible for heartworm disease), both Simparica Trio and NexGard Plus achieved 100% prevention efficacy when administered monthly for six consecutive doses (Source). 

Furthermore, NexGard Plus demonstrated 100% efficacy after a single dose when tested against a susceptible isolate, reinforcing its fast-acting reliability.

Choose between Simparica Trio and NexGard Plus by evaluating your dog’s breed, weight, health profile, and local parasite risks.

In this guide, we’ll go beyond the product labels to help you decide which option aligns best with your dog’s lifestyle, genetic sensitivities, and the specific parasites that pose the greatest threat in your area.

Seasonality, Regional Risk & Parasite Prevention Rotation Strategy

Parasite exposure in dogs varies significantly with climate, geography, and seasonal patterns. In warmer regions like the southern United States, year-round activity of fleas, ticks, and mosquitoes necessitates continuous protection. Conversely, parasite activity typically peaks during spring and summer in northern areas.

Both Simparica Trio and NexGard Plus are designed for monthly administration, providing consistent protection against a broad spectrum of parasites. This regular dosing schedule is crucial, especially in regions with high prevalence of macrocyclic lactone-resistant heartworm strains, such as the Mississippi Delta. 

[Source]

Vets may rotate preventatives with different ingredients to reduce resistance risk.

Understanding Simparica Trio and NexGard Plus for Dogs

Before diving into the differences between Simparica Trio and NexGard Plus, it’s important to understand their core purpose, active ingredients, and how each product targets canine parasites.

Let’s take a closer look at what each offers.

What is NexGard Plus for Dogs?

NexGard Plus is a monthly chewable parasite preventative for dogs that offers protection against fleas, ticks, heartworm disease, and intestinal worms. 

How NexGard Plus works?

NexGard Plus uses a triple-action formula to protect dogs against fleas, ticks, heartworms, and intestinal worms:

• Afoxolaner kills fleas and ticks by overexciting their nervous system, leading to paralysis and death. It acts on GABA receptors, which are essential for nerve signal control in parasites.
• Moxidectin prevents heartworm disease by killing immature heartworm larvae before they can develop into adults.
• Pyrantel paralyzes roundworms and hookworms in the gut, allowing them to be safely passed out in your dog’s stool.

Together, these ingredients offer full-spectrum parasite protection in one chew.

What is Simparica Trio for Dogs?

Simparica Trio is also a broad-spectrum oral flea, tick, and heartworm medication for dogs. It is FDA-approved for puppies as young as 8 weeks and includes the unique advantage of Gulf Coast tick coverage and labeled Lyme disease prevention. . (mention ingredient here)

How Simparica Trio works?

Simparica Trio offers all-in-one parasite control using three powerful ingredients:

• Sarolaner eliminates fleas and ticks by interfering with their nerve function, causing fast-acting paralysis and death. It’s effective against five tick species, including the Gulf Coast tick.
• Moxidectin blocks the development of heartworm larvae in the bloodstream, preventing adult heartworm disease.
• Pyrantel targets intestinal worms by disrupting their nervous system, helping your dog expel them naturally.

This combination makes Simparica Trio ideal for dogs needing reliable monthly protection from multiple parasites.

The efficacy of these two products lies in their active ingredients — all of which are anthelmintics or ectoparasiticides — but each utilizes a different isoxazoline compound for tick and flea control.

Side Effects and Precautions in NexGard Plus and Simparica Trio

While both NexGard Plus and Simparica Trio are FDA-approved and considered safe for most dogs, individual tolerance may vary. Side effects are rare but possible, especially in dogs with pre-existing conditions or breed-specific sensitivities.

• NexGard Plus: Vomiting, diarrhea, lethargy, and in rare cases, seizures.
• Simparica Trio: Vomiting, diarrhea, weight loss, inappetence, and occasional tremors or neurological signs.

Note: Both products contain an isoxazoline (Afoxolaner or Sarolaner), which has been associated — albeit rarely — with neurological side effects, especially in dogs with a history of seizures.

Is NexGard Plus or Simparica Trio Safe for Puppies and Senior Dogs?

Puppies:

• NexGard Plus is safe for puppies 8 weeks or older and ≥4 lbs.
• Simparica Trio is safe for puppies 8 weeks or older and ≥2.8 lbs.

Senior Dogs:

Both products are generally well-tolerated in older dogs, but vets may recommend closer monitoring, especially in dogs with renal, hepatic, or neurological conditions.

Things to Consider before using NexGard Plus or Simparica Trio?

• Neither product is approved for pregnant or lactating dogs.
• Dogs with a known hypersensitivity to isoxazoline-class drugs should not use either.

Always consult your vet before switching preventatives or if your dog is on immunosuppressants, NSAIDs, or long-term corticosteroids.

FDA & Veterinary Safety Notices

Both products are listed in the FDA's Adverse Event Reporting System (AERS) with a strong overall safety profile. However, pet parents are encouraged to report any side effects to their vet and file an adverse event report via the FDA Animal Health portal.

After examining safety profiles and usage precautions, it's equally important to look at how Simparica Trio and NexGard Plus align in functionality. 

What are the Similarities Between NexGard Plus and Simparica Trio for Dogs?

NexGard Plus and Simparica Trio are monthly, vet-prescribed chewables that provide all-in-one protection against fleas, ticks, heartworms, roundworms, and hookworms. Both are FDA-approved for dogs 8 weeks and older. Simparica Trio is approved for dogs as small as 2.8 lbs, while NexGard Plus begins at 4 lbs.

These preventatives replace the need for multiple parasite medications, offering convenience and broad-spectrum coverage in a single dose. The main differences are minor—Simparica Trio includes Gulf Coast tick protection and uses a liver flavor, while NexGard Plus is beef-flavored and treats more hookworm species.

Both options streamline monthly parasite control and suit most dogs depending on weight, flavor preference, and regional parasite risk.

What are the Differences Between Simparica Trio and NexGard plus? 

The main difference between Simparica Trio and NexGard Plus is tick coverage and label claims. Simparica Trio protects against five tick species including Gulf Coast ticks and offers labeled Lyme disease prevention. NexGard Plus treats more hookworm species but lacks Gulf Coast tick and Lyme coverage. Simparica Trio suits smaller dogs; NexGard Plus starts at 4 lbs. 

Tick Species Coverage

• NexGard Plus cover Black-legged tick, American dog tick, Lone star tick, Brown dog tick.
• Simparica Trio cover all of the above, plus the Gulf Coast tick, offering broader U.S. coverage

Hookworm Spectrum

• NexGard Plus cover three species, including Ancylostoma caninum, A. braziliense, and Uncinaria stenocephala
• Simparica Trio covers Ancylostoma caninum and Uncinaria stenocephala

Minimum Weight Eligibility

• Simparica Trio is labeled for dogs as small as 2.8 lbs, making it more suitable for toy breeds.
• NexGard Plus has a slightly higher cutoff at 4 lbs, which may limit early use in extra-small puppies.

Lyme Disease Risk Reduction

• Simparica Trio is labeled for the reduction of Lyme disease transmission through its rapid tick-killing action.
• NexGard Plus currently does not carry this specific indication, though it still protects against the deer tick (Ixodes scapularis), the primary Lyme vector.

NexGard Plus vs Simparica Trio [Side-by-Side Comparison]

Which is More Affordable – NexGard Plus or Simparica Trio?

When it comes to affordability, Simparica Trio generally offers lower pricing across most weight categories, especially for dogs under 45 lbs. While both are premium, prescription-only parasite preventatives, the per-tablet price difference becomes more noticeable for smaller dogs and when buying month-to-month.

Simparica Trio Pricing Based on their Dog's Weight (1 Chewable tablet)

• Simparica Trio Chews for Dogs 2.8 – 5.5 lbs - $36.70
• Simparica Trio Chews for Dogs 5.6 – 11.0 lbs - $37.24
• Simparica Trio Chews for Dogs 11.1 – 22.0 lbs - $37.78
• Simparica Trio Chews for Dogs 22.1 – 44.0 lbs - $41.02
• Simparica Trio Chews for Dogs 44.1 – 88.0 lbs - $42.10
• Simparica Trio Chews for Dogs - 88.1 – 132.0 lbs - $42.64

Most Simparica Trio doses for dogs under 45 lbs are priced under $42, making it a cost-effective option for small to mid-sized breeds that require lower dosing.

It's also a practical choice for multi-dog households with smaller pets, offering flexibility and budget-friendly protection.

NexGard Plus Pricing Based on their Dog's Weight (1 Chewable tablet)

• NexGard PLUS Chews for Dogs 4-8 lbs –  $40.99
• NexGard PLUS Chews for Dogs 8.1-17 lbs –  $39.69
• NexGard PLUS Chews for Dogs 17.1-33 lbs –  $41.99
• NexGard PLUS Chews for Dogs 33.1-66 lbs  - $43.99
  
• NexGard PLUS Chews for Dogs 66.1-132 lbs - $44.99

NexGard Plus starts at nearly $41 even for the smallest dogs, with prices for larger breeds reaching up to $45 per tablet. This makes it slightly more expensive than Simparica Trio across comparable weight categories.

If you're looking to maximize protection without inflating monthly costs:

• Simparica Trio is more cost-effective in small to mid-sized dogs.
  
• Price gaps narrow in larger dogs, where both options exceed $42–$44 per tablet.
  

Pro Tip: Always consider bundling or autoship options on HardyPaw for added savings, and consult your vet to confirm which product aligns best with your dog’s health and exposure risk.

Transition Guide – How to Switch Safely Between Heartworm, Flea & Tick Preventatives

Switching your dog’s parasite prevention plan — whether moving from a combo like Heartgard + NexGard, or transitioning between Simparica Trio and NexGard Plus — requires careful timing and veterinary oversight to avoid gaps in protection or adverse effects.

1. Consult Your Veterinarian First

• Always get vet approval before switching.
  
• Your vet will factor in your dog’s medical history, breed sensitivities, geographic risks, and past medication response.
  
• They’ll also advise on transition timing to avoid overlapping active ingredients or unprotected gaps.
  

2. Follow the “Last Dose + 30 Days” Rule

• Wait 30 days after the last dose of your current preventative before starting a new one.
  
• This ensures that the previous medication’s active ingredient cycle is completed, especially with isoxazolines (e.g., Afoxolaner, Sarolaner).
  
• Starting too early may overload your dog’s system, especially in breeds sensitive to neurological effects.
  

3. Monitor for Reactions After Switching

• Whether switching to Simparica Trio or NexGard Plus, observe your dog for 24–72 hours.
  
• Watch for: vomiting, diarrhea, itching, tremors, or behavioral changes.
  
• If you see anything unusual, report it to your vet immediately.
  

4. Consider a Baseline Heartworm Test

• Especially when switching heartworm medications, a heartworm antigen test ensures your dog isn’t already infected.
  
• Infected dogs need a different treatment plan, and regular preventatives can make diagnosis harder once started.
  

5. Avoid Self-Medicating or Mixing Products

• Don’t “top off” a partially effective product with another.
  
• Avoid mixing Simparica Trio with additional flea/tick products unless specifically advised by your vet.
  
• Never double-dose if you miss a day — just return to the schedule next month.

Breed-Specific Compatibility – Which Preventative Is Best for Your Dog’s Genetics and Size?

Once you've ensured a safe transition between preventatives, the next layer of decision-making comes down to your dog’s genetic predispositions, breed-specific sensitivities, and weight range.

Some dogs — particularly herding breeds and toy-sized companions — may benefit more from one product over the other.

Dogs with MDR1 Gene Sensitivity (Collie-Type Breeds)

• Breeds like Collies, Australian Shepherds, Shelties, and Border Collies can carry a mutation in the MDR1 gene, affecting how their brains process medications.
  
• Both Moxidectin (found in both products) and isoxazolines like Afoxolaner or Sarolaner may cross the blood-brain barrier in MDR1-sensitive dogs.
  

What to Do: If your dog’s breed is prone to MDR1 issues, ask your vet about genetic testing before using either Simparica Trio or NexGard Plus.

Toy and Small Breed Dogs (Under 10 lbs)

• Simparica Trio is approved for dogs as small as 2.8 lbs, making it ideal for breeds like Yorkies, Chihuahuas, and Maltese.
  
• NexGard Plus starts at 4 lbs, which may delay eligibility in extra-small puppies or toy breeds.
  

Palatability Tip: Both products are chewable, but NexGard Plus uses a beef flavor, while Simparica Trio uses liver flavor — consider your dog’s taste preference.

Giant Breeds and Dosing Considerations

• Both products are effective up to 132 lbs, but some extra-large breeds (such as Great Danes, Mastiffs) may require additional dosing consultation.
  
• Simparica Trio comes in more granular dosing options, which may offer a better fit for dogs on the borderline of weight ranges.

Which is Better – Simparica Trio or NexGard Plus?

The answer depends less on which product is “superior” overall and more on which is the best match for your dog’s lifestyle, health profile, and geographic exposure risks.

Choose Simparica Trio If…

• You live in an area with Gulf Coast tick prevalence.
• Your dog weighs between 2.8–4 lbs, and NexGard Plus isn't an option.
• You're seeking a labeled reduction in Lyme disease risk.
• You want broad-spectrum protection with the added benefit of Sarolaner’s extended tick coverage.
  

Choose NexGard Plus If…

• You need enhanced intestinal worm protection, including three hookworm species.
• Your dog has previously tolerated Afoxolaner-based products well (e.g., original NexGard).
• You live in an area where tick species are less diverse, and the Gulf Coast tick isn’t a major concern.
• You prefer a beef-flavored chew over liver (palatability matters for picky eaters).

What Vets Recommend

Most veterinarians will consider:

• Breed-specific tolerances (e.g., isoxazoline sensitivity),
• Geographic parasite exposure, and
• Previous medication history before recommending one over the other.

That’s why your vet’s input remains the most important when choosing between these two top-tier preventatives.

Final Verdict – Should You Choose Simparica Trio or NexGard Plus?

If you're still stuck between Simparica Trio and NexGard Plus, here’s the truth:

💡 You’re not choosing a better product — you’re choosing the better fit.

Both are modern, vet-approved, and clinically proven. What matters more is your dog’s lifestyle, your region’s parasite profile, and how much simplicity you want in your routine. Some dogs need Lyme protection, others need stronger worm defense. Some pet parents value cost per dose, others value tick coverage depth.

Let your vet handle the facts, and your dog’s lifestyle makes the choice.

Simparica Trio Vs NexGard Plus FAQs

Is Simparica Trio safe for dogs with a history of seizures?

Simparica Trio contains Sarolaner, part of the isoxazoline class, which has been linked to rare neurological reactions. If your dog has a seizure history, consult your vet before use. Shop Simparica Trio

Can I switch my dog from Simparica Trio to NexGard Plus mid-cycle?

Yes, but only under veterinary supervision. Avoid overlapping doses. Wait 30 days after the last Simparica Trio tablet before starting NexGard Plus to prevent ingredient stacking and potential side effects.

Do these medications protect against ear mites or mange?

Neither product is labeled for ear mites or mange, though their active ingredients (Sarolaner, Afoxolaner) are sometimes used off-label for mange treatment. Ask your vet before using for skin mite issues.

How long after giving the chew can my dog swim or bathe?

Both Simparica Trio and NexGard Plus are oral treatments, so bathing or swimming won’t reduce effectiveness. Unlike topicals, they remain fully effective even after water exposure.

Are Simparica Trio or NexGard Plus available without a prescription?

No, both are FDA-approved prescription medications. You’ll need a valid vet prescription to order them through trusted sellers like HardyPaw. This ensures safety and correct dosing.

Medical References:

• https://pubmed.ncbi.nlm.nih.gov/39695858/
  
• https://www.fda.gov/animal-veterinary
  
• https://pmc.ncbi.nlm.nih.gov/articles/PMC7049382/