A randomized, multicenter, double-blind, parallel group study was performed to assess the effects of a standardized ginseng extract compared with those of a placebo on quality of life (QoL) and on physiological parameters in symptomatic postmenopausal women. Validated questionnaires [Psychological General Well-Being (PGWB) index, Women's Health Questionnaire (WHQ)] and Visual Analogue (VA) scales were used to assess the effects of the extract on QoL at baseline and after 16 weeks' treatment with either the ginseng extract or placebo. To assess the efficacy of ginseng on postmenopausal symptoms, physiological parameters [follicle-stimulating hormone (FSH) and estradiol levels, endometrial thickness, maturity index and vaginal pH] were recorded at the same time points. Of the 384 randomized patients (mean age 53.5 +/- 4.0 years), the questionnaires were completed by 193 women treated with ginseng and 191 treated with placebo. With regard to the primary endpoint (total score of the PGWB index) the extract showed only a tendency for a slightly better overall symptomatic relief (p < 0.1). Exploratory analysis of PGWB subsets, however, reported p-values < 0.05 for depression, well-being and health subscales in favor of ginseng compared with placebo. No statistically significant effects were seen for the WHQ and the VA scales or the physiological parameters, including vasomotor symptoms (hot flushes). The positive effects of ginseng on health-related QoL in menopausal women should be further investigated. This study shows, however, that the beneficial effects of ginseng are most likely not mediated by hormone replacement-like effects, as physiological parameters such as FSH and estradiol levels, endometrial thickness, maturity index and vaginal pH were not affected by the treatment.