It was performed a prospective randomized study to compare the effectiveness of different medical methods for the prevention of atrial fibrillation (AF) after coronary bypass operations. The study included 158 patients who underwent myocardial revascularization. Patients were divided into 4 groups. Amiodarone was used in the first group (n=50), in the second group (n=50) - propafenone, in the third group (n=28) - phosphocreatine, and there was not antiarrhythmic therapy in the fourth (control) group (n=30). AF was revealed in 13 (26%) patients in the first group, in the second group - in 5 (10%) patients, in the third group - in 5 (17.8%) patients, and in the fourth - in 8 (26.7%) patients. Differences was found between amiodarone and propafenone groups with the advantage of propafenone (p=0.047), as well as the advantage of propafenone in comparison with the control group (p=0.047). The frequency of AF in the phosphocreatine group did not significantly differ from any other groups. However, the analysis of the composite indicator (frequency AF + need for inotropic support) revealed differences between the group of phosphocreatine and control group - 35.7% vs. 63.3% respectively, p=0.036. It was concluded that propafenone is a more effective drug for the prevention of AF in patients after coronary bypass operations than amiodarone. Sinus rhythm recovery in case of propafenone using occurs at an earlier date than with amiodarone due to different pharmacodynamics of the drugs. Using of phosphocreatine in comprehensive prevention of cardiac arrhythmias is promising but it requires further researches.