There is a need for more efficient pharmacological cardioversion of atrial fibrillation (AF). We tested the hypothesis that inhibition of IK1 significantly enhances the efficacy of INa block to depress atrial excitability and to cardiovert AF. The study was conducted in canine isolated arterially-perfused right atrial preparations with rim of ventricular tissue. AF was induced in the presence of acetylcholine (ACh; 0.5 µM). BaCl2 (10 µM) was used to inhibit IK1 and flecainide (1.5 µM) to block INa. Sustained AF (>45 min) was recorded in 100% atria (5/5) in the presence of ACh alone. Flecainide cardioverted AF in 50% of atria (4/8), BaCl2 in 0% (0/5), and their combination in 100% (5/5). AF cardioversion occurred in 15±9 min with flecainide alone (n=4) and in 8±9 min with the combination (n=5). Following drug-induced AF cardioversion, AF was inducible in 4/4 atria with flecainide alone (≤ 5 min duration) and in 2/5 atria with the combination (≤ 30 sec duration). Atrial excitability was significantly more depressed by combined vs. mono- therapies. There was little to no effect on ventricular excitability under any condition tested. Thus, inhibition of IK1 significantly enhances the efficacy of flecainide to depress atrial excitability and to cardiovert AF in our experimental setting. A combination of INa and IK1 inhibition may be an effective approach for cardioversion of AF.