Background: Strong racial discrepancies in end-stage renal disease exist. Whether there are race differences in kidney function loss in younger healthy persons is not well established. Study Design: Longitudinal. Setting & Participants: 3,348 black and white adults with at least 2 measurements of cystatin C-based estimated glomerular filtration rate (eGFRcys) at scheduled Coronary Artery Risk Development in Young Adults (CARDIA) examinations (years 10, 15, and 20). Predictor: Race. Outcomes & Measurements: We used linear mixed models to examine race differences in annualized rates of eGFR cys decline, adjusting for age, sex, lifetime exposure to systolic blood pressure >120 mm Hg, diabetes, and albumin-creatinine ratio. We used Poisson regression to compare racial differences in rapid decline (eGFR cys decline >3% per year) by study period (10-15 years after baseline examination [defining period 1] and >15-20 years after baseline examination [defining period 2]). Results: Mean age was 35 ± 3.6 (SD) years, and mean eGFRcys was 110 ± 20 mL/min/1.73 m2 for blacks and 104 ± 17 mL/min/1.73 m2 for whites at baseline. For both blacks and whites, eGFRcys decline was minimal at younger ages (<35 years) and eGFRcys loss accelerated at older ages. However, acceleration of eGFRcys decline occurred at earlier ages for blacks than whites. Blacks had somewhat faster annualized rates of decline compared with whites, but differences were attenuated after adjustment in period 1 (0.13 mL/min/1.73 m2 per year faster; P = 0.2). In contrast, during period 2, blacks had significantly faster annualized rates of decline, even after adjustment (0.32 mL/min/1.73 m2 per year faster; P = 0.003). The prevalence of rapid decline was significantly higher for blacks versus whites, with prevalence rate ratios of 1.31 (95% CI, 1.04-1.63) for period 1 and 1.24 (95% CI, 1.09-1.41) for period 2. Differences were attenuated after full adjustment: adjusted prevalence rate ratios were 1.20 (95% CI, 0.95-1.49) for period 1 and 1.10 (95% CI, 0.96-1.26) for period 2. Limitations: No measured GFR. Conclusions: eGFRcys decline differs by race at early ages, with faster annualized rates of decline for blacks. Future studies are required to explain the observed differences. © 2013 National Kidney Foundation, Inc.