Background A study was conducted to determine the efficacy and safety of ibutilide fumarate versus placebo in the acute termination of atrial flutter and fibrillation. Methods and Results Two hundred sixty-two patients aged 28 to 88 years with atrial flutter or fibrillation duration of 3 hours to 90 days were randomly assigned in a 5:1 ratio (ibutilide:placebo) to receive two 10-minute infusions, 10 minutes apart, of ibutilide (1 mg) or placebo. Patients were hospitalized and monitored by telemetry for 24 hours, with follow-up 72 hours later. Seventy-three (34.9%) of 209 evaluable ibutilide recipients had termination of atrial flutter or fibrillation within 1.5 hours compared with 0 (0%) of 41 placebo recipients. Those with atrial flutter had a higher success rate. At hour 24, 86.3% remained in normal or alternative sinus rhythm. Of the patients who received ibutilide, 2.3% experienced drug-related sustained polymorphic or monomorphic ventricular tachycardia and recovered after intervention. Additionally, 7.3% experienced nonsustained polymorphic or monomorphic ventricular tachycardia. Other frequent medical events in ibutilide recipients were generally also noted in the placebo group. Conclusions Ibutilide is effective and safe for acute termination of atrial fibrillation or atrial flutter. (Am Heart J 1998;136:632-42.)