High cystatin C levels among patients without clinically recognized chronic kidney disease (CKD) may identify patients who are at preclinical stages of CKD. Higher body mass index (BMI) has been found to be associated with increased risk of CKD. However, the association between BMI and high cystatin C levels is not clear. The authors examined participants older than 20 years from the National Health and Nutrition Examination Survey 1999 to 2002 (N=2583, 50.2% women). BMI was categorized as <25 kg/m2, 25–29.9 kg/m2, and ≥30 kg/m2. Main outcome was high cystatin C (>1 mg/dL) among patients without clinically recognized CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 or microalbuminuria). Higher BMI was positively associated with high cystatin C, independent of age, sex, race-ethnicity, education, smoking, alcohol intake, cholesterol, and C-reactive protein levels. Compared with patients with BMI <25 kg/m2 (referent), the multivariable odds ratio (95% confidence interval) of high cystatin C was 2.53 (1.79–3.58) (Ptrend <.0001 among patients with BMI ≥30 kg/m2). The association between BMI and high cystatin C persisted in subgroup analyses by sex, race-ethnicity, and among those without diabetes or hypertension. Among US adults without clinically recognized CKD, higher BMI levels were independently associated with high cystatin C levels.