OBJECTIVES: To measure the impact of vasomotor symptoms on QoL based on a sample of 1655 healthy, nonhysterectomized, postmenopausal women aged 40 to 65 who were not on hormonal treatment. METHODS: QoL was assessed with the Women's Health Questionnaire (WHQ) and the SF-36. Subgroup analyses were conducted for women with 1) at least 7 moderate to severe hot flushes per day as reported on daily diary cards over a 1-week period; 2) at least one but less than 7 moderate to severe hot flushes per day over the same period; and 3) no hot flushes. RESULTS: Seven percent (7%) of study participants were in subgroup 1.64% in subgroup 2, and 29% in subgroup 3. Women in subgroup 1 had significantly worse scores (p <0.05) than women in subgroup 3 on 8 of 9 WHQ domains (all but attractiveness) and 4 of 8 SF-36 subscales (vitality, bodily pain, social function, and role limitations-emotional) and the mental composite score. Women in subgroup 1 had significantly worse scores (p <0.05) than women in subgroup 2 on 5 WHQ domains (vasomotor symptoms, sleep problems, sexual behavior, somatic symptoms and depressed mood) and 2 SF-36 subscales (vitality and social function). Women in subgroup 2 had significantly worse scores (p <0.05) than women in subgroup 3 on 5 WHQ domains (vasomotor symptoms, sleep problems, somatic symptoms, memory/concentration, and menstrual symptoms) and 2 SF-36 subscales (vitality and role limitations-emotional) and the mental composite score. For each intergroup comparison, absolute score differences for the SF-36 were smaller than those for the WHQ, but always exceeded at least 4 points out of 100 for statistically significant differences. CONCLUSIONS: Women with moderate to severe hot flushes experience a significant decrease in quality of life as measured by the WHQ and SF-36. Wyeth Research supported this project.