Pharmacological therapy for atrial fibrillation (AF) is difficult because AF induces atrial remodeling. Randomized prospective studies using amiodarone could not show the superiority of rhythm control strategy to rate control strategy for treatment of AF. Bepridil is a multichannel blocker like amiodarone and expected to be effective for termination of AF without exacerbation of extracardiac adverse effects. Efficacy and safety of bepridil in pharmacological cardioversion of long-lasting AF (≥3 months) was assessed. To avoid the risk of excessive QT prolongation, bepridil dosage was limited to ≤200 mg/day and aprindine (class Ib) was added if necessary. Bepridil alone or in combination with aprindine restored sinus rhythm in 69% of patients. No adverse effects necessitating drug termination occurred. The average time to conversion after starting bepridil was 30 days and cardioversion was associated with significant increase in fibrillation cycle length. After cardioversion, atrial contraction recovered faster within 1 week and sinus rhythm was maintained better than conventional electrical cardioversion. The history of drug-resistant AF did not affect efficacy of bepridil. These observations suggest that pharmacological cardioversion of long-lasting AF could become a new therapeutic option. Although the precise mechanism of cardioversion by bepridil is not clear, reversal of the remodeled atria may play an important role.