OBJECTIVES: To determine whether vasomotor symptom reduction is associated with improved work productivity using pooled data from 2 clinical trials for the relief of menopausal hot flushes with desvenlafaxine succinate (DVS). METHODS: A total of 843 postmenopausal women experiencing 50 or more moderate-to-severe hot flushes per week received 100 or 150 mg/day DVS or placebo in 2 randomized, double-blind, placebo-controlled trials. Subjects kept daily hot flush and sleep diaries and completed the Profile of Mood States (POMS) and Work Limitations Questionnaire (WLQ) at baseline and week 12. To control for multiplicity, the data were analyzed using multivariate analysis of covariance (MANCOVA), adjusting for age, race, type of menopause, and baseline values. RESULTS: At both 100-and 150-mg doses, DVS reduced the number and severity of hot flushes from baseline to week 12 compared with placebo (all comparisons, P<0.0001). DVS reduced the number of nighttime awakenings due to hot flushes (P<0.0001) and improved self-perceived sleep quality (P<0.05) at both doses compared with placebo. The 100 mg dose also significantly increased the daily number of minutes slept (P<0.05). POMS total mood disturbance score improved significantly in both DVS dose groups compared with placebo (P<0.001). Work limitation, measured by WLQ total index score, decreased significantly from baseline to week 12 in subjects treated with 100 mg DVS (adjusted mean [SE] reduction= -3.3 [0.9]; P=0.0115) compared with placebo (-1.4 [0.9]). The 100 -mg dose group had significant improvement on the time management (P=0.0354), mental-interpersonal (P=0.0034), and output demand (P=0.0174) subscales. For the 150 -mg group, the reduction in WLQ total index score approached significance (-2.9 [0.9]; P=0.0545) and the mental-interpersonal improved significantly compared with placebo (P=0.0057). CONCLUSION: Reductions in hot flush frequency and severity and improved sleep and mood are accompanied by significant improvement in work productivity in postmenopausal women treated with DVS.