Background Radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (AF) is still challenging even in RFCA-era for AF. The aim of this study was to assess the clinical utility of nifekalant, a pure potassium channel blocker, during RFCA for persistent AF. Methods and results We retrospectively enrolled 157 consecutive persistent AF patients undergoing first RFCA procedure with complex fractionated atrial electrogram (CFAE) ablation after pulmonary veins isolation and compared outcomes between patients with (NFK group: N=79) and without (No-NFK group: N=78) additional CFAE ablation using intravenous nifekalant (0.3mg/kg). Primary endpoint was 24-month atrial arrhythmia-free survival post ablation. The prevalence of AF termination was significantly higher in NFK group than No-NFK group (64.6% versus 7.7%, P<0.001). Arrhythmia-free survival, however, was not significantly different between 2 groups (61.5% versus 54.1%, P=0.63). There was no significant difference between 2 groups in the prevalence of recurrent atrial tachycardia (25.0% versus 23.5%, P=0.89). Arrhythmia-free survival in patients with AF termination during procedure was significantly higher than those without (73.0% versus 41.0%, P=0.002; adjusted hazard ratio 0.48, 95% confidence interval 0.17-0.84, P=0.02) among NFK group, but not among No-NFK group (66.7% versus 53.2%, P=0.53). Conclusions Intravenous nifekalant injection during additional CFAE ablation did not improve sinus maintenance rate after RFCA procedure for AF, but AF termination by nifekalant injection could be a clinical predictor of better success rates after procedure.