Vasomotor symptoms (VMS), including hot flashes and night sweats, are common among postmenopausal women and are associated with reduced health related quality of life (HRQOL).To determine whether Veterans are more likely to report VMS than non-Veterans, and whether the association of VMS with HRQOL varies by Veteran status.We used data from the Women's Health Initiative Observational Study, including self-reported baseline VMS presence and severity, and HRQOL at follow-up Year 3 (RAND Short Form 36-Item Health Survey). Employing generalized linear models we estimated whether Veteran status was associated with any VMS. We estimated the association between any VMS and HRQOL using linear regression, stratified by Veteran status. Interaction terms were added separately to determine whether the association varied by baseline depression, obesity, or smoking status.The final analyses included 77,153 postmenopausal women (2,004 Veterans). After adjustment, Veterans were no more likely than non-Veterans to report any VMS at baseline (relative risk [RR] 0.97, 95% confidence interval [CI] 0.90-1.04) or moderate to severe VMS (RR 1.03, 95% CI 0.89-1.18). Any VMS was associated with decreased HRQOL at Year 3, particularly among Veterans (mean difference range: Veterans -2.7 to -4.6, p-values < .001; non-Veterans -2.2 to -2.6, 95% CI -0.13 to -0.09, p values < .001). Baseline depression and obesity, but not smoking, amplified the negative association between VMS and HRQOL.Multicondition care models for postmenopausal Veteran and non-Veteran women are needed that incorporate management strategies for VMS, weight, and depression.