The purpose of this study was to compare climacteric symptoms associated with health-related quality of life (HRQOL) among women from Madrid (Spain) and Belgrade (Serbia). A cross-sectional study included 461 women from Madrid and 513 women from Belgrade aged 40–65 years. Climacteric symptoms and HRQOL were examined using the Menopause Rating Scale (MRS). There were no differences in MRS total score (p = 0.873), somato-vegetative and urogenital domain scores regarding country groups. However, women from Belgrade had poorer psychological domain score than women from Madrid (p = 0.027). Madrilenian women were more likely to have worse MRS score if they were coupled, had gynaecological complaints and longer duration of amenorrhoea. In Belgradian women, having higher level of education and using hormone-replacement therapy was associated with worse MRS score. Midlife women from Madrid and Belgrade had similar perception of intensity of urogenital and somato-vegetative climacteric symptoms. Belgradian women, however, perceived psychological symptoms as more severe. IMPACT STATEMENT What is already known on this subject? Social and cultural meanings of menopause vary across countries. It is quite delicate to strike a balance between two or more populations of women that can be compared, but also have specific features that are unique to their area. Similarities such as position of women in the society, access to education, contraception and safe induced abortion can facilitate this comparison. What do the results of this study add? Spanish and Serbian women rated similarly somato-vegetative and urogenital complaints, but Serbian women had worse psychological symptoms compared to Spanish women. Spanish women were more likely to endure climacteric symptoms until they withdraw spontaneously. Serbian women of higher education were more likely to use hormone-replacement therapy to manage climacteric complaints. What are the implications of these findings for clinical practice and/or further research? This study is the first to compare climacteric symptoms between women in Spain and Serbia. Despite the universality of menopause, culture seems to play a major role in differences in the perception of specific climacteric symptoms. Examination of quality of life in menopausal transition is an important measure of health status and should become a part of the routine health care in midlife.