OBJECTIVE We evaluated the safety and efficacy of ibutilide when added to propafenone in treating both paroxysmal and chronic atrial fibrillation (AF) and atrial flutter (AFL). BACKGROUND The effects of ibutilide in patients with paroxysmal or chronic AF/AFL who were pre-treated with propafenone have not been previously evaluated. METHODS Oral propafenone was initially given in 202 patients with AF/AFL without left ventricular dysfunction. Intravenous ibutilide was administered in 104 patients in whom propafenone failed to convert the arrhythmia. Two different propafenone dosage regimens were used according to the duration of the presenting arrhythmia: patients with paroxysmal arrhythmia (n = 48) received 600 mg loading dose, and patients with chronic arrhythmia (n = 56) were receiving 150 mg three times a day as stable-dose pre-treatment. RESULTS Ibutilide offered an overall conversion efficacy of 66.3% (69 of 104 patients), 70.8% for patients with paroxysmal AF/AFL and 62.5% for patients with chronic AF/AFL. Ibutilide significantly decreased the heart rate (HR) and further prolonged the QTc interval (p < 0.0001). The degree of HR reduction after ibutilide administration emerged as the sole predictor of successful arrhythmia termination (p < 0.001). After ibutilide, one patient (1%) developed two asymptomatic episodes of non-sustained torsade de pointes, and 10 patients (9.6%) manifested transient bradyarrhythmic events; however, all bradyarrhythmic effects were predictable, occurring mostly at the time of arrhythmia termination. None of 82 patients who decided to continue propafenone after successful cardioversion had immediate arrhythmia recurrence. CONCLUSIONS Our graded approach using propafenone and ibutilide appears to be a relatively safe and effective alternative for the treatment of paroxysmal and chronic AF/AFL to both rapidly restore sinus rhythm in nonresponders to monotherapy with propafenone and prevent immediate recurrences of the arrhythmia.