Background: Tibolone is frequently used as a hormone-like alternative to traditional HRT. Therefore, it is valuable to compare the effects of tibolone and HRT on cardiovascular diseases risk factors. Methods: A total of 156 healthy non-surgical postmenopausal women were included in an open randomized study. They were assigned to receive daily 2.5 mg tibolone plus one Cal+D (500 mg calcium and 200 IU vitamin D) tablet (n=52), 0.625 mg conjugated equine estrogen and 2.5 mg medroxy progesterone (CEE/MPA) plus one Cal+D tablet (n=52), or one Cal+D tablet (n=52). The latter group was used as control. The women were followed for six months. The body mass index (BMI), blood pressure (BP), serum levels of high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride (TG), C reactive protein (CRP), sex hormone binding globulin (SHBG), free testosterone index (FTI), and free estradiol index (FEI) were determined before and after the interventions. Results: Compared to baseline values, BMI, BP, CRP, SHBG, HDL, FTI, and FEI were significantly different after the treatments in the tibolone and CEE/MPA receiving groups (P<0.05 ), but not in the control group. Moreover, serum LDL and TG levels changed significantly after the treatments in all the three groups (P<0.01). There were significant differences between the tibolone and CEE/MPA groups in terms of CRP, LDL, HDL, TG, SHBG, FTI, FEI and BP (P<0.01). Conclusion: Tibolone may be considered an alternative to conventional HRT in postmenopausal women. However, clinical recommendations regarding the effects of tibolone on cardiovascular outcome needs further studies.