Objectives The results of the studies in which the effect of hormone replacement therapy (HRT) on cardiac function have been evaluated are rather disputable. In these studies, cardiac function was evaluated with conventional echocardiographic methods. This study was planned in order to investigate the effects of HRT on myocardial velocities and myocardial performance index (MPI) in healthy early postmenopausal women. Method In a prospective, controlled study, 60 healthy postmenopausal women were assigned to two groups (32 in the HRT group and 28 in the control group). After conventional echocardiographic parameters were measured, tissue Doppler echocardiography recordings were obtained from the mitral and tricuspid annulus. Systolic myocardial velocity (Sm), early and late diastolic myocardial velocities (Em and Am) and time intervals were measured and MPI was calculated. Then the symptom-limited exercise stress test using the Bruce protocol was performed. After 3 and 6 months of HRT (oral 0.625mg conjugated estrogen + 2.5mg medroxyprogesterone acetate/day), the same examinations were repeated. The effects of HRT on myocardial velocities, MPI and exercise time were evaluated at the 3rd and 6th months. Results The parameters of the control group remained statistically unchanged during the study. HRT did not have any effect on segmental and mean left ventricular (LV) Sm or right ventricular (RV) Sm. However, LV Em/Am and RV Em/Am ratios significantly increased at the 6th month of HRT, and LV and RV MPI values were observed to decrease significantly as compared to basal values. Additionally, a significant increase was observed in exercise duration and metabolic equivalent values after 3 months of HRT, and this increase continued at the 6th month as well. The favorable changes in all parameters in the HRT group were significantly different from those of the control group. Conclusion Data obtained in this study suggest that HRT is not only effective for treating menopausal complaints but also increases cardiovascular performance by improving especially diastolic functions in early postmenopausal women. © 2010 International Menopause Society.