OBJECTIVE: To examine the relationships of race/ethnicity, menopausal status, health characteristics, and symptoms with use of 21 types of complementary and alternative medicine (CAM) in midlife women. DESIGN: Cross-sectional, multiple logistic regression analyses of 2,118 women completing the sixth annual visit in the Study of Women’s Health Across the Nation, a multisite, multiethnic, longitudinal study. RESULTS: More than half of women used some type of CAM. Use of most types of CAM differed significantly by race/ethnicity, except the use of ginkgo biloba and glucosamine. Significantly more African Americans at most sites and Chinese women used ginseng. Use of most types of CAM did not differ significantly by menopausal status or vasomotor symptoms, except the use of soy supplements, which was significantly greater among women who reported vasomotor symptoms. Women reporting somatic symptoms were significantly more likely to use glucosamine. Women reporting psychological symptoms were significantly more likely to use ginkgo biloba and soy supplements. The number of comorbidities, moderate or high socioeconomic status, number of healthy behaviors, symptom sensitivity, age, and dietary genistein intake were significantly positively associated with use of several types of CAM. CONCLUSIONS: The use of most types of CAM is not related to menopausal status or symptom reporting but to sociodemographic factors, comorbidities, and health behaviors. Given the large proportion of midlife women who use CAM and the potential for interactions with prescribed medications, healthcare practitioners should inquire about CAM use and be aware of which factors influence the use of different types of CAM.