The aim of this study was to examine the association of vasomotor symptoms (VMS) with anxiety and/or depressive symptoms in perimenopausal women. A retrospective chart review of 487 women 40 to 64 years old seen during October 2004 to December 2006 in the Women's Midlife Assessment Program at the University of California, Davis, was performed. Of these, 395 women were included in the analysis: 58 (15%) were premenopausal, 199 (50%) were perimenopausal, and 138 (35%) were postmenopausal. VMS bothersomeness was represented by converting Likert-scale ratings for hot flashes and night sweats to scores and adding them into an overall score. Multiple logistic regression models were used to quantify the association of self-reported anxiety and/or depressive symptoms with VMS bothersomeness. Thirty-one (53%) premenopausal, 131 (66%) perimenopausal, and 69 (50%) postmenopausal women reported anxiety and/or depressive symptoms. Perimenopausal and postmenopausal women reporting anxiety and/or depressive symptoms had significantly higher VMS bothersomeness scores (2.2 +/- 1.7 and 2.2 +/- 1.9, respectively) than did women who did not report these symptoms (1.7 +/- 1.7 and 1.6 +/- 1.7, respectively; both P values < 0.05). Women experiencing more bothersome VMS were significantly more likely to report anxiety and/or depressive symptoms (odds ratio, 1.5; P < 0.01). Perimenopausal women were significantly more likely to report anxiety and/or depressive symptoms than were postmenopausal women (odds ratio, 1.9; P < 0.01). Both associations remained significant after restricting the analyses to women not taking hormone therapy or psychotropics. VMS bothersomeness was associated with self-reported anxiety and/or depressive symptoms, showing the importance of screening for anxiety and mood changes during perimenopause.