In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine, 239 patients with paroxysmal atrial fibrillation were prospectively treated with flecainide (n = 122) or quinidine (n = 117) in an open-label, randomized trial. All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects. Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation (difference, p = 0.282; not significant), fewer flecainide patients had to have their therapy discontinued due to adverse experiences (p = 0.012). Based on both endpoints (efficacy and tolerability), an estimated 70.5% of flecainide versus 55.4% of quinidine patients would remain effectively treated at the end of 1 year on therapy (p < or = 0.007). The findings of this prospective study suggest that in the treatment of paroxysmal atrial fibrillation (1) flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation; (2) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects; and (3) given the overall endpoint of efficacy and tolerability, more patients are likely to continue long-term therapy with flecainide than with quinidine.