Objectives: This study aimed to compare the efficacy of tibolone and transdermal estrogen in treating menopausal symptoms in postmenopausal women with an intact uterus. Methods: Overall, 26 women consumed tibolone orally and 31 women received transdermal estrogen gel mixed with progestogen. The menopause rating scale (MRS) was used to assess their menopausal symptoms at their first outpatient visit and 6 months later. Results: The transdermal estrogen group showed significant improvements in more items of the MRS questionnaire. There was a favorable change in body weight in the transdermal estrogen group compared with that in the tibolone group. Depressive mood, irritability, physical and mental exhaustion, sexual and bladder problems, and joint and muscular discomfort improved only in the transdermal estrogen group, whereas heart discomfort and vaginal dryness improved only in the tibolone group. Nevertheless, the intergroup differences in each item were insignificant after adjusting for body mass index and hypertension, which differed before treatment. Conclusions: Both the therapeutic options improved menopausal symptoms within 6 months of use. However, transdermal estrogen appeared to be more effective in preventing weight gain in menopausal women than tibolone.