This audit examined outcomes for 203 patients prescribed zonisamide (ZNS) for various uncontrolled seizure types at a specialist outpatient service. Forty-two (20.7%) patients achieved 6 months of seizure freedom, and an additional 37 (18.2%) had a 50% seizure reduction for 6 months on a stable ZNS dose. Seizure freedom was more likely in patients with primary generalized (24/61, 39%) than in those with partial-onset (18/141, 12.7%) seizures (P<0.001). Eight patients (5 seizure free) were maintained on ZNS monotherapy. More patients became seizure free with ZNS as monotherapy or first add-on, compared with those in whom ZNS was the second, third, or fourth adjunctive drug (P=0.001). Seizure freedom was less likely in patients treated with hepatic enzyme-inducing agents (13/113, 11.5%) than in those receiving noninducing AEDs (24/82, 29.3%) (P=0.002). ZNS was discontinued in 72 (35.5%) patients largely because of side effects (n=58, 28.6%). Commonest complaints leading to withdrawal were sedation (n=14), nausea and vomiting (n=13), neuropsychiatric symptoms (n=12), rash (n=6), and weight loss (n=6). Around 80% of patients who became seizure free on ZNS or had the drug withdrawn did so on a dose 200mg. ZNS is an effective broad-spectrum AED that can also produce a range of dose-dependent and idiosyncratic side effects.