We aimed to evaluate the effectiveness and safety of dronedarone versus sotalol in real-world practice in Asian patients with atrial fibrillation (AF). Using the Korean nationwide claims database from August 2013 to December 2016, we identified patients with AF recently prescribed dronedarone or sotalol and analyzed the hospitalization risk and all-cause death until December 2017. Overall, 3119 and 1575 patients treated with dronedarone and sotalol, respectively, were included. After propensity score weighting, no significant differences were observed between the treatment groups. Dronedarone use was associated with a lower risk of all-cause hospitalization than sotalol use (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.70–0.88). The dronedarone group demonstrated a significantly lower risk of cardiovascular (CV) hospitalization than the sotalol group (HR 0.62, 95% CI 0.53–0.72); however, no significant difference was observed in non-CV hospitalization. No difference in the risk of all-cause death was observed between groups. The dronedarone group was significantly less likely to receive nonpharmacological treatment for AF than the sotalol group (HR 0.63, 95% CI 0.51–0.77). In a large-scale population of Asian patients with AF, dronedarone was associated with a lower risk of CV hospitalization and a lower need for nonpharmacological treatment for AF than sotalol.