Class III antiarrhythmic drugs have been shown to be effective for termination of atrial fibrillation (AF). The aim of this study was to determine the steady state and non-steady state effects of amiodarone and ibutilide on the atrial monophasic action potential (MAP) duration (MAPD), effective refractory period (ERP), and intra-atrial conduction time (IACT) in human persistent AF.Fourteen patients with persistent AF who underwent internal atrial defibrillation were included in the study. The atrial MAP was recorded at the high right atrium. IACT was measured from the pacing spike to the distal coronary sinus. MAPD and IACT were assessed during the steady state and at the shortest diastolic interval (DI) at a basic cycle length (CL) of 600 msec and after a premature stimulus. Amiodarone did not affect MAPD or the ERP at the basic CL, but it increased MAPD at the shortest DI. Amiodarone increased IACT at both the basic CL and the shortest DI. Ibutilide increased the MAPD and ERP at the basic CL and at the shortest DI. Ibutilide did not affect IACT at the basic CL or the shortest DI.Ibutilide increases atrial MAPD not only in the steady state but also at the shortest DI, but it does not affect IACT in patients with persistent AF. Amiodarone does not affect MAPD or ERP, but it increases IACT in the steady state, and it increases MAPD and IACT at the shortest DI.