The long-term effects of zonisamide as monotherapy or adjunctive therapy were investigated in patients with seizure disorders. One hundred twelve adult neurology patients treated with zonisamide were retrospectively identified through a chart review; 90 patients (n=45 monotherapy, n=45 adjunctive therapy) who received zonisamide for 3 months were included in the efficacy-evaluable population, and all 112 patients were included in the safety population. The average duration of treatment was 24.3 months (range, 3-46 months), and the average zonisamide dosage was 324 mg/day (range, 100-1000 mg/day). Thirty-eight of 90 patients (42%; n=25 monotherapy, n=13 adjunctive therapy) were seizure-free, and an additional 26 patients (29%; n=9 monotherapy, n=17 adjunctive therapy) had 50% seizure frequency reduction at the last follow-up visit. Thirty of 112 patients (27%) reported mild to moderate adverse events, such as weight loss (5.4%), fatigue (4.5%), and sedation (2.7%). Zonisamide, as monotherapy or adjunctive therapy, was a safe, effective, and well-tolerated long-term treatment option in patients with various seizure types.