Introduction: This study was designed to evaluate safety and efficacy of combined low dose aspirin and warfarin therapy following mechanical heart valve replacement. Methods: A total of 1496 patients (686 males, mean age 35 +/- 8.5 years) undergoing mechanical heart valvular replacement were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) group. International normalized ratio (INR) and prothrombin time was maintained at 1.8-2.5 and 1.5-2.0 times of the normal value, respectively. Thromboembolic events and major bleedings were registered during follow up. Results: Patients were followed up for 24 +/- 9 months. The average dose of warfarin in the study and control group was 2.92 +/- 0.87 mg and 2.89 +/- 0.79 mg, respectively (p>0.05). The overall thromboembolic events in study group were lower than in control group (2.1% vs. 3.6%, p=0.044). No statistically significant differences were found in hemorrhage events (3.5% vs. 3.7%, p>0.05) or mortality (0.3% vs 0.4%, p>0.05) between the two groups. Conclusions: Following mechanical valve replacement, combined low dose aspirin and warfarin therapy was associated with a greater reduction in thromboembolism events than warfarin therapy alone. This combined treatment was not associated with an increase in the rate of major bleeding or mortality. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.