Background Existing drug therapies for paroxysmal supraventricular tachycardia (PSVT) have potentially serious adverse effects. Dofetilide, a pure class III antiarrhythmic agent, may offer an effective and safe alternative for treating PSVT. This study compared the efficacy and safety of dofetilide with that of propafenone and placebo in the prevention of PSVT. Methods This multicenter, randomized, placebo-controlled, parallel-group study compared the effectiveness of oral dofetilide 500 μg given twice daily with that of propafenone 150 mg given 3 times a day and placebo in preventing the recurrence of PSVT in 122 symptomatic patients. Episodes of PSVT were documented by symptom diaries and Hertcard (Hertford Medical, Hertfordshire, UK) event recorders. Results After 6 months of treatment, patients taking dofetilide, propafenone, and placebo had a 50%, 54%, and 6% probability, respectively, of remaining free of episodes of PSVT (P <.001 for both dofetilide and propafenone vs placebo). Both dofetilide and propafenone also decreased the frequency of episodes of PSVT; the median numbers of episodes in the dofetilide- and propafenone-treated groups were 1 and 0.5, respectively, compared with 5 in the placebo-treated group. Dofetilide was well tolerated; no proarrhythmia occurred. Three patients taking propafenone had serious treatment-related adverse effects that required drug discontinuation. Conclusions Dofetilide and propafenone were equally effective in preventing the recurrence of or decreasing the frequency of PSVT. (Am Heart J 2001;142:93-8.)