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Importance: Women often experience physiological and functional changes in their health during midlife. Identifying women who have clinically important improvements in physical health and function and evaluating the factors associated with these improvements can identify intervention targets at midlife., Objective: To identify factors associated with improvements in physical health and function among women during midlife., Design, Setting, and Participants: Participants were part of the Study of Women's Health Across the Nation (SWAN), a diverse cohort of US women early in midlife, and followed up annually for up to 21 years between 1996 and 2017. Analyses were based on visit 8 (2004-2006) through visit 15 (2015-2017). Statistical analysis was conducted from October 2021 to March 2023., Exposures: Sociodemographic indicators, health status measures, and comorbidities measured at visit 8., Main Outcomes and Measures: The main outcome was a clinically important (≥5 points) improvement in the physical component score (PCS) of the 36-item Short-Form Health Survey between visit 8 and visit 15., Results: Of the 1807 women (at visit 8: mean [SD] age, 54.5 [2.7] years; 898 [50%] White participants) in SWAN who qualified for analysis, 265 (15%) experienced a clinically important improvement in PCS over a median of 11.1 years (IQR, 10.9-11.4 years). Factors associated with improvement in PCS included no financial strain (odds ratio [OR], 1.73; 95% CI, 1.18-2.52), no sleep disturbances (OR, 1.43; 95% CI, 1.05-1.96), no osteoarthritis (OR, 1.42; 95% CI, 1.01-1.99), and having a higher physical activity score (OR, 1.17; 95% CI, 1.00-1.37) as assessed at visit 8. Women who had a higher PCS at visit 8 (OR, 0.84; 95% CI, 0.83-0.86), who had a higher body mass index (OR, 0.95; 95% CI, 0.93-0.97), or who were taking more medications (OR, 0.93; 95% CI, 0.88-0.98) had lower odds of an improved PCS., Conclusions and Relevance: This cohort study of women in midlife suggests that approximately 15% of women experienced clinically important improvements in health and function over an 11-year period. Several potentially modifiable factors associated with improvements may inform women of variables to target for future interventions.