The long-term effect of implantable vagus nerve stimulators (VNS) on seizures has not been evaluated in epileptic dogs. Report seizure frequency in medication-resistant epileptic dogs before and after VNS implantation. Twelve client-owned dogs with idiopathic epilepsy and >1 seizure day per 3 weeks despite 3 months of appropriate use of 2 antiseizure medications and seizure diaries maintained 6 months before and >12 months after VNS implantation. Uncontrolled, open-label, before and after study. Mean monthly seizures and inter-seizure periods obtained from contemporaneous seizure diaries in the 6 months before implantation were compared with 0 to 6 months, 7 to 12 months, and subsequent 12-month periods after implantation. The number of dogs with >50% decrease in seizure frequency, >3 times increase in inter-ictal period interval, and seizure freedom for >3 months at the time of death or last follow-up were recorded. Five of 12 dogs were euthanized <12 months after implantation. All 7 remaining dogs showed >50% decrease in seizure frequency until last follow-up, starting at a median of 37 to 48 months after implantation (range, 0-6 to 61-72 months) and a >3-fold increase in mean inter-seizure interval starting a median of 25 to 36 months after implantation (range, 0-6 months to 49-60 months), 3/7 dogs were seizure-free at death or last follow-up. Monthly seizure frequencies decreased and inter-seizure intervals increased in all dogs 2 to 3 years after VNS implantation, but a high proportion were euthanized before this time point. Prospective clinical trials are required to establish causality and the magnitude of this association.