Abstract Background Glycated albumin (GA) is a short-term measure of glycemic control. Several studies have demonstrated an inverse association between body mass index (BMI) and GA, which may affect its performance as a biomarker of hyperglycemia. We investigated cross-sectional associations between GA and multiple measures of adiposity, and compared its performance as a glycemic biomarker by obesity status, in a nationally representative sample of US adults. Methods We measured GA in adults from the 1999–2004 National Health and Nutrition Examination Survey. Separately in adults with and without diabetes, we assessed associations of GA with adiposity measures (BMI, waist circumference, trunk fat, total body fat, and fat mass index) in sex-stratified multivariable regression models. We compared sensitivity and specificity of GA to identify elevated hemoglobin A1c (HbA1c), by obesity status. Results In covariate-adjusted regression models, all adiposity measures were inversely associated with GA in adults without diabetes (β=−0.48 to −0.22%-point GA per 1 SD adiposity measure; n = 9750) and with diabetes (β=−1.73 to −0.92%-point GA per SD). Comparing adults with vs without obesity, GA exhibited lower sensitivity (43% vs 54%) with equivalent specificity (99%) to detect undiagnosed diabetes (HbA1c ≥ 6.5%). Among adults with diagnosed diabetes (n = 1085), GA performed well to identify above-target glycemia (HbA1c ≥ 7.0%), with high specificity (>80%) overall but lower sensitivity in those with vs without obesity (81% vs 93%). Conclusions Inverse associations between GA and adiposity were present in people with and without diabetes. GA is highly specific but may not be sufficiently sensitive for diabetes screening in adults with obesity.