Objective:To investigate the effects of low dose tibolone short-term therapy on clinic, endocrine and markers of cardiovascular disease in healthy postmenopausal women.Methods: A prospective study involved a total of 42 eligible postmenopausal women. 22 cases as group A and 20 cases as group B. Complete baseline work-up including Kupperman score,body mass index (BMI), gonadotropin (FSH, LH), estrogen (E2), testosterone (T), sex hormone binding globulin (SHBG), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA), high-sensitivity C-response protein (hs-CRP), nitrogen oxide (NO)and fasting lipid, glucose(FPG), insulin(FINS) were performed in all subjects. Postmenopausal women in group A were treated with 1.25 mg tibolone daily. Women in group B were treated with 0. 625 mg tibolone daily. Women both in group A and group B were given calcium 600 mg with vitamin D 125IU per day. At the end of the 12-weeks therapy, subjects were re-evaluated and above parameters were measured.Results:No significant differences between group A and group B were found at baseline.Twenty-eight cases (fourteen cases in each group) completed the study. Kupperman score decreased from (22.1±8.0) and (25.4±7.5) to (7.7±4.5) and (5.2±4.5) and plasminogen activator inhibitor type 1 decreased from (95.8±32.4)μg/L and (102.9±42.6)μg/L to (72.2±39.6)μg/L and (79.9±30. 1) μg/L significantly in group A and group B respectively after treatment. In group A, Blood pressure decreased significantly from (120 ± 10)/(83 ± 6) mmHg to (110±14)/(77± 9) mmHg (P＜0.05), testosterone increased significantly from (0. 6 ±0. 4)nmol/L to (1.3 ± 1.1) nmol/L (P＜0. 05), free testosterone increased from (0. 001 ±0. 002)nmol/L to (0. 003±0. 003) nmol/L significantly (P＜0.01), SHBG decreased from (7.6±4. 9)nmol/L to (4. 3±2.9) nmol/L significantly (P＜0.05), total cholesterol decreased from (5.4±0. 8) mmol/L to (5.0±0.8) mmol/L significantly (P＜0.01), ApoA decreased from (1.8±0.3)mg/dl to (1.7±0. 3) mg/dl significantly (P＜0.05), fasting glucose decreased from (5. 6±0.8)mmol/L to (3.9±1.1) mmol/L significantly (P＜0.01) and no significant differences in BMI,FSH, LH, E2, tPA, hs-CRP, NO, TG, HDL-C, LDL-C, apoB were found after treatment. In group B, there were no significant differences in other parameters found after treatment except Kupperman score and PAI-1.Conclusions: 1.25 mg/d tibolone short-term therapy was associated with improved fibrinolytic factors and decreased Kupperman score, blood pressure, total cholesterol and fasting blood glucose level. 0. 625 mg/d tibolone therapy resulted in decrease Kupperman score and improvement of fibrinolytic factors. These changes relieve climacteric symptoms and may have some benefits on preventing the development of cardiovascular disease. An increased testosterone and free testosterone levels in 1.25 mg dose of tibolone therapy may increase energy level, general wellbeing and sexual desire in postmenopausal women. Low dose tibolone replacement therapy is a convenient effective HRT for postmenopausal women