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Background: Tibolone is frequently used as a hormone-likealternative to traditional HRT. Therefore, it is valuable tocompare the effects of tibolone and HRT on cardiovasculardiseases risk factors.Methods: A total of 156 healthy non-surgical postmenopausalwomen were included in an open randomized study. They wereassigned to receive daily 2.5 mg tibolone plus one Cal+D (500mg calcium and 200 IU vitamin D) tablet (n=52), 0.625 mgconjugated 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 werefollowed for six months. The body mass index (BMI), bloodpressure (BP), serum levels of high density lipoprotein (HDL),low-density lipoprotein (LDL), and triglyceride (TG), C reactiveprotein (CRP), sex hormone binding globulin (SHBG), freetestosterone index (FTI), and free estradiol index (FEI) weredetermined before and after the interventions.Results: Compared to baseline values, BMI, BP, CRP, SHBG,HDL, FTI, and FEI were significantly different after thetreatments in the tibolone and CEE/MPA receiving groups(P<0.05 ), but not in the control group. Moreover, serum LDLand TG levels changed significantly after the treatments in allthe three groups (P<0.01). There were significant differencesbetween 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 toconventional HRT in postmenopausal women. However, clinicalrecommendations regarding the effects of tibolone on cardiovascularoutcome needs further studies.Iran J Med Sci 2010; 35(4): 281-286.