Azimilide is a potassium channel antagonist that, in contrast to existing class III antiarrhythmic agents, blocks both the rapidly (I(Kr)) and slowly (I(Ks)) activating components of the delayed rectifier potassium current. In animal and clinical studies, azimilide prolonged repolarisation by increasing the action potential duration and effective refractory period. In animal models, azimilide was effective in terminating both atrial and ventricular arrhythmias. Azimilide also demonstrated antifibrillatory efficacy in a canine model of sudden cardiac death. In patients with a history of atrial fibrillation/flutter, oral azimilide controlled arrhythmias more effectively than placebo in a 6-month randomised double-blind study. At a dosage of 125 mg once daily, azimilide significantly increased the time to first symptomatic recurrence of atrial fibrillation/flutter. However, no significant difference between placebo and azimilide was found in another study. Oral azimilide 100 mg once daily demonstrated clinically significant treatment effects in patients with paroxysmal supraventricular tachycardia. In clinical trials, azimilide was generally well tolerated and headache was the most commonly occurring adverse event. Azimilide is associated with a low incidence of proarrhythmic events, such as torsades de pointes, and few serious adverse events have been reported.