Simparica Trio vs Heartgard Plus - What’s Best for Your Dog?

Pet parents are often faced with this critical decision when choosing the most effective and comprehensive protection against internal and external parasites. 

Several FDA-approved oral treatments like Proheart12, Nexgard Plus, Revolution, Advantage Multi, Bravecto along with Simparica Trio and Heartgard Plus are there to protect dogs from heartworm disease, intestinal worms like roundworms and hookworms, and—depending on the option—external threats such as fleas and ticks. 

While they serve a similar core purpose, their active ingredients (sarolaner, moxidectin, pyrantel, and ivermectin), parasite coverage spectrum, and safety profiles differ significantly. 

Understanding these differences is essential for optimizing your dog’s health, especially in regions with year-round parasite exposure or during peak mosquito and tick seasons.

When selecting a parasite prevention plan, it’s important to look beyond brand names and assess how each treatment aligns with your dog’s needs. 

Factors like geographic parasite prevalence, age and weight suitability, ingredient sensitivity, and outdoor activity level influence which product is the better fit. 

In this guide, we’ll provide an in-depth comparison of Simparica Trio and Heartgard Plus so you can make an informed, vet-aligned decision tailored to your pet’s unique health profile.

Understanding Simparica Trio and Heartgard Plus

Before diving into comparisons, it’s essential to understand what each medication offers, how they work, and why veterinarians recommend them for parasite prevention in dogs.

Simparica Trio for Dogs: Broad-Spectrum Protection in a Single Chew

Simparica Trio is a prescription-only, once-a-month chewable tablet that combines three active ingredients—sarolaner, moxidectin, and pyrantel—to provide triple-layer protection. 

• Sarolaner: Targets and kills adult fleas and multiple species of ticks (Lone Star, Gulf Coast, American dog, and deer ticks) within hours of administration.
• Moxidectin: Works systemically to prevent heartworm disease by eliminating immature heartworm larvae transmitted by mosquitoes.
• Pyrantel :  Treats and controls intestinal parasites, specifically roundworms and hookworms, which are common in puppies and dogs exposed to contaminated environments.

Important Considerations

• Minimum Age/Weight: Approved for use in dogs 8 weeks and older, weighing at least 2.8 pounds.
• Not evaluated in breeding, pregnant, or lactating dogs—consult your veterinarian before use.
• Chewable & Palatable: Liver-flavored tablet that most dogs accept easily.
• Prescription required.

Simparica Trio Side Effects:

• Most common: Vomiting, diarrhea, lethargy, and decreased appetite
• Rare: Tremors, seizures (especially in dogs with a history of neurological issues)
• Monitor after first dose; contact vet if symptoms persist

Heartgard Plus for Dogs: Trusted Protection for Heartworms and Intestinal Worms

Heartgard Plus is one of the most widely prescribed heartworm preventatives in the U.S. It uses two active ingredients—ivermectin and pyrantel—to offer focused protection against internal parasites.

• Ivermectin: A macrocyclic lactone that kills immature heartworm larvae before they reach the bloodstream and mature into dangerous adult worms.
• Pyrantel: Provides effective treatment for hookworms and roundworms, which can cause weight loss, diarrhea, and digestive issues in dogs.

Important Considerations

• Minimum Age/Weight: Safe for dogs 6 weeks and older, with no minimum weight restriction.
• Approved for breeding, pregnant, and lactating dogs—ideal for growing or reproductive pets.
• No flea or tick protection.
• Prescription required.

Heartgard Plus Side Effects:

• Most common: Vomiting, diarrhea, and loss of appetite
• Rare: Depression, ataxia (loss of coordination), or seizures—usually linked to ivermectin sensitivity in herding breeds
• Generally well-tolerated, even in pregnant, nursing, and young dogs

Difference between Simparica Trio and Heartgard Plus - A Comparison Table

The main difference between Simparica Trio and Heartgard Plus is that Simparica Trio protects against fleas, ticks, heartworms, roundworms, and hookworms, while Heartgard Plus only protects against internal parasites like heartworms, roundworms, and hookworms.

Now that you’ve seen how Simparica Trio and Heartgard Plus stack up side by side, the next step is understanding how parasite risks vary by region and season—and how that impacts your choice.

Parasite activity isn't constant throughout the year, and where you live plays a major role in determining what level of protection your dog truly needs. Let’s explore the U.S. parasite risk map to guide your timing and treatment decisions more precisely.

Cost Comparison: Simparica Trio vs. Heartgard Plus by Weight

Simparica Trio costs $36.70 to $42.64 monthly, depending on weight, covering both internal and external parasites. Heartgard Plus costs $11.59 to $14.19 monthly and protects only against internal parasites.

Choosing between Simparica Trio and Heartgard Plus isn’t just about parasite coverage—it’s also about value for money. The following pricing chart compares monthly costs based on your dog’s weight so you can assess the most cost-effective option for your needs.

Simparica Trio (All-in-One Protection) -Fleas, ticks, heartworms, roundworms & hookworms

Heartgard Plus (Internal Parasite Defense Only) - Heartworms, roundworms & hookworms

HardyPaw Tip: Simparica Trio may replace the need for additional flea/tick treatments, saving money long term, while Heartgard Plus is an excellent budget option for internal protection only.

Now, the next step is understanding how parasite risks vary by region and season—and how that impacts your choice. 

Parasite activity isn't constant throughout the year, and where you live plays a major role in determining what level of protection your dog truly needs. Let’s explore the U.S. parasite risk map to guide your timing and treatment decisions more precisely.

Seasonal Parasite (Heartworm) Risk Map for Dogs (U.S. Regions)

Parasite activity isn’t uniform across the country, and skipping prevention during “off” months can leave pets vulnerable. 

[Image Source]

In the U.S., heartworm disease affects more than 1 in 100 dogs annually, with prevalence reaching up to 6.5% in some parts of the Southeast  (Source: American Heartworm Society). 

Ticks, on the other hand, affect over 50% of dogs in high-risk areas like the Northeast and Midwest (Source: CAPC).

Understanding these regional patterns helps tailor your prevention strategy—whether that means year-round coverage or seasonal adjustments based on where you live and your dog’s exposure risk.

Regional Risk Zones:

• Southeast & Gulf Coast (FL, TX, LA): Year-round risk for fleas, ticks, and heartworms.
• Midwest (OH, IL, MO): Spring to fall activity; mosquito spikes in summer.
• Northeast (NY, NJ, MA): High Lyme disease risk from ticks; fleas peak in warmer months.
• Southwest (AZ, NM): Year-round flea concerns; ticks are prevalent in rural areas.
• Pacific Northwest (WA, OR): Ticks and heartworms are rising with climate shifts.

[Source]

HardyPaw Tip: Use this information to time preventatives wisely—but for most U.S. regions, year-round protection is safest.

Understanding your region’s parasite exposure is just one part of the equation. If you’re considering changing your dog’s medication based on new seasonal risks or broader protection needs, making the switch safely is key.

Even a small lapse in coverage can leave your pet vulnerable. Here’s how to transition between Heartgard Plus and Simparica Trio without missing a beat.

Transition Guide - How to Switch Safely Between Heartworm Preventatives

Thinking of switching from Heartgard Plus to Simparica Trio—or vice versa? 

Safely switch between Simparica Trio and Heartgard Plus by waiting 30 days after the last dose, consulting your vet, and monitoring for side effects. Never overlap treatments unless directed by a veterinarian.

Step-by-Step Transition Guide:

• Consult your veterinarian before switching to ensure no health contraindications.
• Wait until the current cycle ends. Do not double-dose.
• Administer the new treatment exactly 30 days after the last one.
  
• If you switch from Heartgard Plus to Simparica Trio, your dog will now receive added flea and tick protection.
• Always monitor for side effects during the first dose transition.
• Keep up with heartworm testing every 12 months regardless of brand.

Key Tip: Never mix preventatives unless specifically instructed by a veterinarian, as ingredient overlap may cause toxicity.

Factors to Consider When Choosing Between Simparica Trio and Heartgard Plus

While both medications offer strong parasite protection, selecting the most suitable option for your dog requires evaluating several personalized factors. This section outlines real-world decision points that influence which treatment may be the better fit.

1. Geographic Risk and Parasite Prevalence

If you live in a region with high flea and tick activity—such as wooded areas, humid climates, or rural zones—Simparica Trio is often the preferred choice. Its added protection against external parasites makes it more appropriate for dogs with regular outdoor exposure.

In contrast, Heartgard Plus may be adequate for dogs in low-risk urban or suburban areas, where tick and flea infestations are less common and heartworm protection is the main concern.

2. Lifestyle and Activity Level

Active dogs that frequently go hiking, camping, or spend time at dog parks are at higher risk for external parasite exposure. Simparica Trio’s broader spectrum is ideal in these scenarios. For mostly indoor or senior dogs with limited outdoor contact, Heartgard Plus may suffice as a targeted internal parasite preventive.

3. Reproductive Status

If your dog is pregnant, nursing, or intended for breeding, Heartgard Plus is the safer choice. It has a well-established safety profile for use in these life stages, whereas Simparica Trio has not been tested for breeding or pregnant dogs.

4. Dog Size and Weight-Based Dosing

Choosing the right dosage is crucial for safe and effective parasite protection. Both Simparica Trio and Heartgard Plus offer chewable tablets tailored to your dog’s weight.

🟨 Simparica Trio – Broad-spectrum monthly protection against heartworms, fleas, ticks, roundworms, and hookworms:

• Simparica Trio for Dogs 2.8–5.5 lbs (Gold Box) – Ideal for the smallest pups needing all-in-one protection.
• Simparica Trio for Dogs 5.6–11.0 lbs (Purple Box) – Perfect fit for small dogs with active lifestyles.
• Simparica Trio for Dogs 11.1–22.0 lbs (Caramel Box) – Comprehensive defense for mid-size dogs.
• Simparica Trio for Dogs 22.1–44.0 lbs (Teal Box) – Trusted monthly coverage for medium-sized breeds.
• Simparica Trio for Dogs 44.1–88.0 lbs (Green Box) – Designed for large dogs exposed to high parasite risk.
• Simparica Trio for Dogs 88.1–132.0 lbs (Brown Box) – Maximum-strength protection for extra-large dogs.

🟦 Heartgard Plus – Monthly prevention for heartworms, roundworms, and hookworms:

• Heartgard Plus for Small Dogs up to 25 lbs (Blue Box) – Vet-trusted option for small dogs and puppies.
• Heartgard Plus for Medium Dogs 26–50 lbs (Green Box) – Safe and effective for mid-size dogs needing internal parasite protection.
• Heartgard Plus for Large Dogs 51–100 lbs (Brown Box) – Ideal for large breeds requiring reliable heartworm defense.

5. Budget Considerations

While Simparica Trio typically costs more per dose, it can be more cost-effective in the long run because it eliminates the need for a separate flea and tick preventative. Heartgard Plus may be more affordable upfront but may require additional treatments to ensure complete parasite protection.

6. Veterinarian Guidance

Always consult your veterinarian to evaluate:

• Your dog’s medical history
  
• Any breed-specific sensitivities
  
• Risk exposure based on your location and climate
  

Beyond lifestyle and location, breed-specific traits can also influence which product is safest and most effective.

Some breeds have unique sensitivities or physical characteristics that impact how they respond to certain active ingredients. 

The following compatibility matrix breaks it down by breed type to help you make an even more personalized decision.

Breed-Specific Compatibility Matrix

Certain breeds have sensitivities or weight considerations. Here's what you need to know:

Note: Always consult your vet for breed-specific dosing, especially in genetically sensitive dogs.

Final Verdict: Simparica Trio or Heartgard Plus?

Which one is the best for my dog?

• Choose Simparica Trio if your dog needs broad-spectrum protection—especially if fleas and ticks are a concern.
  
• Opt for Heartgard Plus if your dog is young, pregnant, lactating, or mainly indoors and you want targeted protection against heartworms and intestinal worms.
  

Always consider factors like lifestyle, location, and health history when making the decision.

Still not sure which one to pick? At HardyPaw, we help pet parents make confident, vet-backed choices for their dogs’ health. Visit our Dog Heartworm Preventives Collection to explore other trusted brands for Heartworm medicine, compare products, and get exclusive member discounts.

Visit our Coupon Codes and Discounts page to access current promotions and save on your next purchase of Simparica Trio or Heartgard Plus.

Protect smarter—choose HardyPaw for reliable, personalized parasite protection that puts your dog’s health first.

Heartgard Plus vs Simparica Trio FAQs

Can Simparica Trio and Heartgard Plus be used together?

No, using both together may cause ingredient overlap. Simparica Trio already contains moxidectin and pyrantel, making Heartgard Plus redundant and potentially risky.

Does Simparica Trio kill mites or mange-causing parasites?

Simparica Trio targets fleas and ticks but does not treat sarcoptic mange or ear mites. Your vet may prescribe sarolaner-only Simparica for mite infestations.

Is Heartgard Plus safe for Collies or herding breeds?

Heartgard Plus is safe for most herding breeds, even those with MDR1 gene sensitivity, due to its low ivermectin dose, but always confirm with a vet.

How long after giving Simparica Trio is my dog protected?

Protection begins within 4 hours for fleas and 8 hours for ticks, lasting 30 days. Heartworm prevention acts retroactively over the past month.

What should I do if my dog vomits after taking the chewable?

If vomiting occurs within 1 hour of dosing, re-administer the tablet. Contact your vet if symptoms persist or side effects escalate.

Can Simparica Trio prevent Lyme disease?

By killing Lyme-carrying ticks like the deer tick, Simparica Trio lowers risk, but it’s not a vaccine. Annual Lyme shots may still be needed.

How do I know if the treatment is working?

Monitor for flea or tick presence and follow up with annual heartworm testing to verify protection efficacy per veterinary guidelines.

Is it okay to switch from Heartgard Plus to Simparica Trio?

Yes, switch only under veterinary supervision. Ensure timing aligns to maintain continuous heartworm coverage and avoid overlap.

References:

• https://amc-la.com/parasite-prevention-control/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC7049388/
• https://pubmed.ncbi.nlm.nih.gov/32660542/
• https://www.capcvet.org/maps
• https://www.heartwormsociety.org/pet-owner-resources/heartworm-basics