Because cardiovascular disease is the leading cause of death and hypoalbuminemia predicts mortality, hypoalbuminemia may be associated with atherosclerosis. In 1,411 patients enrolled in the HEMO study, associations of albumin with the presence of coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral vascular disease (PVD), and any one of the three conditions at baseline were examined using multivariable logistic regression models. In the two-slope model, when albumin level was 3.6 g/dL (36 g/L) or greater, with each 1-g/dL (10-g/L) increase in albumin level the odds for CAD (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.17 to 0.59), PVD (OR, 0.39; 95% CI, 0.18 to 0.80), CVD (OR, 0.33; 95% CI, 0.15 to 0.73), and any one of the three conditions (OR, 0.23; 95% CI, 0.12 to 0.44) decreased. When albumin level was less than 3.6 g/dL (36 g/L), none of the conditions was statistically significantly associated with each 1-g/dL (10-g/L) increase in albumin level. When normal- and low-albumin groups were compared with each other, patients with albumin levels less than 3.6 g/dL (36 g/L) had a higher association with CAD (OR, 1.32; 95% CI, 1.03 to 1.70) and for any one of the three conditions (OR, 1.38; 95% CI, 1.07 to 1.78). The odds for atherosclerosis linearly decreased as albumin level increased in the normal-albumin group, and a plateau was seen in the low-albumin group; however, the low-albumin group had significantly greater CAD. The nonlinearity of association of albumin level with prevalence of atherosclerosis might be due to the cross-sectional nature of the study of higher mortality with hypoalbuminemia. Copyright 2002 by the National Kidney Foundation, Inc.