Hormone replacement therapy (HRT) is a standard approach to medical care for patients with gender incongruence. HRT is aimed at suppression of primary and secondary sex characteristics of the sex assigned at birth and development of characteristics of the desired sex. HRT in trans women (TW) usually consists of estrogen preparations and antiandrogens. Epidemiological studies demonstrate that HRT reduces gender dysphoria, improves psycho-social outcomes and health-related quality of life. However, concerns about safety of this therapy are widespread both among patients and doctors. The systematic review seeks to elucidate the impact of feminizing HRT on risks of cancer, venous thromboembolism (VTE) and osteopenia among TW. Systematic search in Web of Science, Scopus and PubMed with keywords: “transgender” OR “transsexual” OR “gender dysphoria”, as well as “cancer”; “thromboembolism” OR “thromboembolic”; “osteoporosis” OR “bone”. Results: (a) Feminizing HRT does not enhance risks of cancer among TW. Slight increase in cancer prevalence can probably be attributed to lifestyle factors, especially smoking. (b) Modern schemes of feminizing HRT that do not contain ethinylestradiol are safe with regards to VTE. There's not enough data to understand the relationship between progestines and VTE risks. Continuation of HRT during the perioperative period probably does not increase risks of VTE during and after the surgery. (c) Results for impact of feminizing HRT on bone health are mixed. Suppression of androgens without replacement with estrogens clearly reduces bone mineral density (BMD) both among adults and adolescents.