Summary: Postmenopausal hormone replacement therapy (HRT) has usually been evaluated the relationship with atherosclerotic disease, whereas its effect on direct cardiac functions hasn't been investigated in detail. This study was planned to investigate the long-term effects of HRT on cardiac functions and exercise performance. Methods: Thirty-six postmenopausal women (mean age: 51±4 years, 39-60 years) were prospectively analyzed with pulsed wave Doppler echocardiography and symptom-limited exercise stress test before HRT (oral 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesteron acetate/day), and at the third and the sixth months. The effect of HRT on left ventricular ejection fraction (EF), early filling velocity (E wave) and late filling velocity (A wave), E wave deceleration time (EDT), E/A ratio, myocardial performance index (MPI), exercise duration and METS changes were examined. Results: HRT did not significantly alter the left ventricular EF. At the third month of HRT, there was an insignificant increase in E wave, EDT, and E/A ratio, whereas an insignificant decrease was noted in MPI (P>0.05). However, at the sixth month of HRT, these changes became significant (68±12 vs. 75±13 cm/s, P<0.01; 171±24 vs. 184±14 ms, P<0.01; 1.01±0.23 vs. 1.11±0.27, P<0.01, and 44±9 vs. 39±8%, P<0.001, respectively). On the other hand, exercise duration and exercise METS values showed significant improvements at the third month of HRT (423±104 vs. 482±104 s, P<0.001; 8.2±1.7 vs. 9.1±2 METS, P<0.001). These improvements also continued at the sixth month of HRT. In conclusion, postmenopausal HRT leads to a progressive improvement on left ventricular function parameters, and in parallel, in exercise performance. © 2003 Elsevier Ireland Ltd. All rights reserved.