Background Identifying potentially modifiable risk factors is critically important for reducing the burden of chronic kidney disease. We sought to examine the association of body mass index (BMI) with kidney function decline in a cohort of young adults with preserved glomerular filtration at baseline. Study Design Longitudinal cohort. Setting & Participants 2,839 black and white young adults with cystatin C-based estimated glomerular filtration rate (eGFRcys) > 90 mL/min/1.73 m2 taking part in the year-10 examination (in 1995-1996) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Predictor BMI, categorized as 18.5-24.9 (reference), 25.0-29.9, 30.0-39.9, and ≥40.0 kg/m2. Outcomes Trajectory of kidney function decline, rapid decline (>3% per year), and incident eGFRcys < 60 mL/min/1.73 m2 over 10 years of follow-up. Measurements GFRcys estimated from the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation for calibrated cystatin C at CARDIA years 10, 15, and 20. Results At year 10, participants had a mean age of 35.1 years, median eGFRcys of 114 mL/min/1.73 m2, and 24.5% had BMI ≥ 30.0 kg/m2. After age 30 years, average eGFR cys was progressively lower with each increment in BMI after adjustment for baseline age, race, sex, hyperlipidemia, smoking status, and physical activity. Higher BMI category was associated with successively higher odds of rapid decline (for 25.0-29.9, 30.0-39.9, and ≥40.0 kg/m2, adjusted ORs were 1.50 [95% CI, 1.21-1.87], 2.01 [95% CI, 1.57-2.87], and 2.57 [95% CI, 1.67-3.94], respectively). 18 participants (0.6%) had incident eGFRcys < 60 mL/min/1.73 m2. In unadjusted analysis, higher BMI category was associated with incident eGFRcys < 60 mL/min/1.73 m2 (for 25.0-29.9, 30.0-39.9, and ≥40.0 kg/m 2, ORs were 5.17 [95% CI, 1.10-25.38], 7.44 [95% CI, 1.54-35.95], and 5.55 [95% CI, 0.50-61.81], respectively); adjusted associations were no longer significant. Limitations Inability to describe kidney function before differences by BMI category were already evident. Absence of data for measured GFR or GFR estimated from serum creatinine level. Conclusions Higher BMI categories are associated with greater declines in kidney function in a cohort of young adults with preserved GFR at baseline. Clinicians should vigilantly monitor overweight and obese patients for evidence of early kidney function decline. © 2014 by the National Kidney Foundation, Inc.