Behavioral strategies are recommended for menopausal symptoms, but little evidence exists regarding efficacy.Describe design and methodology of a randomized controlled 3 by 2 factorial trial of yoga, exercise and omega-3 fatty acids.Women from three geographic areas with a weekly average of ≥14 hot flashes/night sweats, who met exclusion/inclusion criteria, were randomized to 12weeks of: 1) yoga classes and daily home practice; 2) supervised, facility-based aerobic exercise training; or 3) usual activity. Women in each arm were further randomized to either omega-3 supplement or placebo. Standardized training, on-going monitoring, and site visits were adopted to ensure consistency across sites and fidelity to the intervention. Participant adherence to the intervention protocol was monitored continuously, and retention was actively encouraged by staff. Information on adverse events was systematically collected.Of 7377 women who responded to mass mailings, 355 (4.8%) were randomized; mean age was 54.7 (sd=3.7), 26.2% were African American, 81.7% were post-menopausal, and mean baseline frequency of daily hot flashes/night sweats was 7.6 (sd=3.8). Adherence of ≥80% was 59% for yoga, 77% for exercise training, and 80% for study pills. Final week 12 data were collected from 95.2%Conducting a multi-site, multi-behavioral randomized trial for menopausal symptoms is challenging but feasible. Benefits included cost-effective study design, centralized recruitment, and methodologic standardization.