ABSTRACT Objectives: To investigate the effect of individual-level, neighborhood, and environmental variables on uterine fibroid (UF) prevalence in a Chicago-based cohort. Methods: Data from the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) were analyzed. Individual-level variables were obtained from questionnaires, neighborhood variables from the Chicago Health Atlas, and environmental variables from NASA satellite ambient air exposure levels. The Shapiro-Wilks test, logistic regression models, and Spearman’s correlations were used to evaluate the association of variables to UF diagnosis. Results: We analyzed 602 participants (mean age: 50.3±12.3) who responded to a question about UF diagnosis. More Black than White participants had a UF diagnosis (OR, 1.32; 95% CI, 0.62–2.79). We observed non-significant trends between individual-level and neighborhood variables and UF diagnosis. Ambient air pollutants, PM2.5 and DSLPM were protective against UF diagnosis (OR 0.20, CI: 0.04–0.97: OR 0.33, CI: 0.13–0.87). Conclusions: Associations observed within a sample in a specific geographic area may not be generalizable and must be interpreted cautiously.