INTRODUCTION Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short‑duration atrial fibrillation (AF). However, there are no data on the comparison of antazoline and antiarrhythmic drugs listed in clinical guidelines. OBJECTIVES The aim of the study was to assess the comparative effectiveness and safety of antazoline‑based and propafenone‑based strategies in pharmacological cardioversion of short‑duration AF performed in our emergency department. PATIENTS AND METHODS We conducted a retrospective case‑control study based on the analysis of medical records of patients undergoing pharmacological cardioversion of short‑duration AF with intravenous antazoline or propafenone at our department in the years 2008-2012. The primary endpoint was the successful cardioversion of AF. The primary safety endpoint was hospitalization due to the adverse effects of the treatment. RESULTS We analyzed 432 cases of cardioversion. The mean age of patients was 68.9 ±9.8 years; 65% of the patients were male; 90% of the patients had a history of AF. Antazoline was administered 334 times and propafenone-98 times. The mean dose of antazoline was 172 ±65 mg, while all patients in the propafenone group received the drug at a fixed dose of 70 mg (1 vial). Cardioversion with antazoline was successful in 239 cases (71.6%) and with propafenone-in 54 patients (55.1%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.07-1.57). The rate of hospitalization due to the adverse effects of the treatment were low and similar between the study groups: 10 (3.0%) for antazoline and 4 (4.1%) for propafenone (RR, 0.73; 95% CI, 0.23-2.27). CONCLUSIONS The antazoline‑based strategy was more effective and safer in comparison with propafenone‑based strategy in the pharmacological cardioversion of short‑duration AF in our emergency department.