BACKGROUND AND AIM: Phthalates may disrupt energy balance in animals, but their effects in humans remain uncertain. We examined whether phthalate exposure was associated with body fat gain in midlife women. METHODS: We analyzed longitudinal data from 1369 women in the Study of Women’s Health Across the Nation Multi-Pollutant Study. Eleven phthalate metabolites measured in spot urine samples at baseline (1999/2000) were standardized with covariate-adjusted creatinine. Body weight (BW), percent body fat (BF%), and waist-to-hip ratio (WHR) were measured near-annually until 2016/2017. For each metabolite, linear mixed effects models with interaction terms between time and log₂(metabolite) were used to predict outcomes, adjusting for demographic, lifestyle, and menopause-related factors. Analyses were conducted overall and stratified by baseline obesity status due to heterogeneity in outcome trajectories. All analyses were repeated using a second set of metabolites measured in 2002/2003 to evaluate findings’ robustness. RESULTS:In all women, metabolites of di(2-ethylhexyl) phthalate (DEHP), monobenzyl phthalate (MBzP), mono-carboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) were associated with faster increases in BF%. The difference in the rate of change per doubling of metabolites ranged from 0.012 percentage point (pp)/year (95% confidence interval (CI): 0.00014, 0.023) for MBzP to 0.019 pp/year (95% CI: 0.0044, 0.033) for MCPP. Stratified analyses revealed that positive associations occurred primarily in women who were normal/underweight at baseline, where mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), MBzP, and MCPP were associated with faster increases in all outcomes. For instance, each doubling of MnBP was associated with 0.091% (95% CI: 0.0025, 0.18), 0.029 pp/year (95% CI: 0.0083, 0.049), and 0.025% (95% CI: 0.0020, 0.047) faster increases in BW, BF%, and WHR, respectively. Most associations were attenuated and non-significant when using exposure data from 2002/2003. CONCLUSIONS:Some phthalate metabolites were associated with fat gains in midlife women, but results may be sensitive to the timing of exposure. KEYWORDS: Phthalates, Endocrine disrupting chemicals, Obesity and metabolic disorders, Female, Environmental epidemiology