ABSTRACT: To explore the link between depressive symptoms and fracture in midlife women, this study employed both cross-sectional and retrospective cohort analyses, a crucial step in identifying those at risk of fractures. The cross-section study data (n = 1940) were retrieved from the baseline assessment of the Study of Women's Health Across the Nation. In the retrospective cohort study (n = 1884), women's Center for Epidemiologic Studies Depression scores were assessed at the start, and their fracture status was recorded during a 5-year follow-up. Logistic regression models were applied to explore the connections between depressive symptoms and fractures in both cross-sectional and retrospective cohort studies. Among 379 women with fracture and 1561 without, depression could not predict fracture based on both Center for Epidemiologic Studies Depression scores (P = .216) and depressive symptoms (P = .883) after adjusting for age, body mass index, smoking, menopausal status, spine and hip bone mineral density, race/ethnicity, total family income, education, physical activity, financial strain, medication use, and history of diseases. However, among 1884 women in the retrospective cohort study, depressive symptoms was associated with a 53.6% increase in fracture risk after adjustment (odds ratio 1.536, 95% confidence interval 1.051-2.245, P = .027). Moreover, a high proportion of women with depressive symptoms was found in the fracture group, and women with depressive symptoms at the start showed a statistically significant correlation with the number of fractures. Depressive symptoms can serve as a predictor for fractures in midlife women 5 years later, independent of health and physiological factors, yet no clear link was found in the cross-sectional analysis.