OBJECTIVES: Use of postmenopausal hormone replacement therapy (HRT) has been associated with an elevated risk of gynecological cancers. There is evidence that the effect differs with the type of hormone used. Dydrogesterone is pharmacologically very similar to progesterone. METHODS: We used the UK-based General Practice Research Database (GPRD) to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing breast, ovarian, endometrial/uterine or cervical cancer in estradiol/dydrogesterone (E/D) users, users of other HRT, or non-users of HRT. RESULTS: The breast cancer incidence rates were 2.41 (95% confidence interval (CI) 1.81-3.15), 3.28 (95% CI 3.01-3.55) and 3.16 (95% CI 2.92-3.42) per 1000 person-years for E/D users, users of other HRT or non-users, respectively. In a direct comparison, the breast cancer risk for E/D users was lower than for users of other HRT (odds ratio 0.76, 95% CI 0.56-1.05). The incidence rates of other gynecological cancers were similar or also slightly lower for E/D users than for users of other HRT. CONCLUSION: This study provides evidence that the risk of developing gynecological cancers with E/D use of several months to a few years is similar to the risks of developing gynecological cancer without HRT or use of other HRT.