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Heartworm disease in domestic dogs is a preventable disease caused by infection with the parasite, Dirofilaria immitis, that can lead to severe pulmonary and cardiac disease. Prevention is through consistent use of FDA-approved heartworm preventive (HWP) products. Banfield® Pet Hospital (Banfield PH), the largest network of primary care small animal hospitals in the United States, carries 11 HWP products for dogs in its formulary. Preliminary research provide evidence that rates of “breakthrough” infections differ by the route of HWP product administration and that (previously) infected dogs that were treated to clear the infection are still at higher risk of cardiac disease later in life, emphasizing importance of prevention. A cost-effectiveness analysis was conducted to evaluate HWP product categories, based on their route of administration, and owner lifetime cost to prevent and/or treat heartworm infection with years-of-life gained (YLG) as the outcome. Comparing injectable extended release (6- or 12-month) products and monthly topical or oral products to receipt of no HWP product, the analysis revealed that expected owner costs and patient outcome did not differ greatly between the product categories with an estimated gain of 1.4 months of life if they received HWP products. The incremental cost-effectiveness analysis estimates that average dog owner cost of $7,500+ per YLG regardless of product category. Evaluating reasonable cost for HWP products for a disease that may cost $3,000+ (out-of-pocket) to treat is difficult, as willingness-to-pay thresholds or accepted estimates for value of a pet’s life beyond fair market value have not been established. While no obvious indication that HWP product categories are more cost-effective, the analysis demonstrates the potential of this approach to compare individual products to inform decision-making for product selection and pricing in Banfield PH and the veterinary industry.