Significant mortality occurs in populations with chronic kidney disease (CKD), but the relative contributions of lower glomerular filtration rate (GFR) itself, accompanying comorbidities, and the numerous abnormalities that develop with advancing CKD are poorly studied. We examined all-cause predialysis mortality in 861 United States veterans with CKD stage 3 to 5 not yet on dialysis. The association of GFR with mortality was analyzed by the Kaplan-Meier method, and the effects of several confounding variables on mortality were assessed in a Cox proportional-hazards model. Overall death rate was 102.1/1,000 person-years (95% CI: 90.2 to 115.6). Lower kidney function was associated with higher mortality (relative risk [95%CI] for GFR less than 20 v 41 to 60 mL/min/1.73 m2: 2.56 [1.61 to 4.07], P<0.001) after adjustment for age, race, diabetes mellitus, cardiovascular disease, smoking status, body mass index, mean arterial pressure, serum albumin, blood cholesterol, haemoglobin, and 24-hour urine protein. For every 10 mL/min/1.73 m2 lower estimated GFR, the adjusted relative risk of mortality (95% CI) was 1.28 (1.12 to 1.45), P<0.001. Lower kidney function is associated with increased mortality in patients with moderate and advanced CKD. This association is present even after adjustment for several confounders.