The aim of this study was to analyze the effect of participation in a mindfulness training program (mindfulness-based stress reduction, [MBSR]) on the degree of bother from hot flashes and night sweats.This study was a randomized trial of 110 late perimenopausal and early postmenopausal women experiencing an average of 5 or more moderate or severe hot flashes (including night sweats)/day. A wait-list control (WLC) was used with 3-month postintervention follow-up. The main outcome was the degree of bother from hot flashes and night sweats in the previous 24 hours. Secondary measures were hot flash intensity, quality of life, insomnia, anxiety, and perceived stress.Baseline average (SD) hot flash frequency was 7.87 (3.44) and 2.81 (1.76) night sweats/day. Mean (SD) bothersomeness score was 3.18 (0.55; "moderately bothered/extremely bothered"). All analyses were intention to treat and were controlled for baseline values. Within-woman changes in bother from hot flashes differed significantly by treatment arm (week × treatment arm interaction, P = 0.042). At completion of the intervention, bother in the MBSR arm decreased on average by 14.77% versus 6.79% for WLC. At 20 weeks, total reduction in bother for MBSR was 21.62% and 10.50% for WLC. Baseline-adjusted changes in hot flash intensity did not differ between treatment arms (week × treatment arm interaction, P = 0.692). The MBSR arm made clinically significant improvements in quality of life (P = 0.022), subjective sleep quality (P = 0.009), anxiety (P = 0.005), and perceived stress (P = 0.001). Improvements were maintained 3 months postintervention.Our data suggest that MBSR may be a clinically significant resource in reducing the degree of bother and distress women experience from hot flashes and night sweats.