OBJECTIVE To assess prospectively the relationship between microalbuminuria and mortality in a geographically defined population of NIDDM patients and to determine the relative importance of microalbuminuria as a risk factor for mortality. RESEARCH DESIGN AND METHODS A survey of known diabetes undertaken in 1982 identified a cohort of 249 NIDDM patients. Follow-up information was available for 246 patients who contributed 1498 person-yr exposure and were followed up for a mean period of 6.1 yr. The median age of the cohort at entry was 68 yr (range 28-89 yr), and the median duration of diabetes was 7 yr (range 1-41 yr). At baseline, a clinical examination was performed and a random daytime urine specimen was obtained for measurement of urinary albumin concentration. RESULTS UAC results were available for 236 patients: 45 (19%) patients had a UAC > 15- < 40 mg/L; 36 (15%) had a UAC 40-200 mg/L; 10 (4%) had a UAC > 200 mg/L; and 145 (61%) had a normal UAC < or = 15 mg/L. During the follow-up period, 93 patients died. All-causes mortality, expressed as standardized mortality ratio (SMR = 149) and coronary heart disease mortality (CHD SMR = 166) were significantly increased. This excess mortality was significant in women (all-causes SMR = 194, CHD SMR = 234) but not in men (all-causes SMR = 118, CHD SMR = 128). On univariate analysis, systolic blood pressure was the only significant association with albumin concentration (P = 0.0002). An age-stratified log-rank test was conducted to determine the effect of potential explanatory variables on survival. Survival distributions were significantly different for known duration of diabetes (P = 0.045), intermittent claudication (P = 0.012), severity of retinopathy, lens opacity (P < 0.001) and UAC (P = 0.013) and diastolic blood pressure approached significance (P = 0.051). After adjusting for the effects of these potentially confounding variables identified by the log-rank analysis, significant predictors of early mortality on multivariate survival analysis were age, UAC of 40-200 mg/L (relative risk = 2.2, 95% confidence interval 1.3-3.7), more severe retinopathy (relative risk = 3.4, 95% confidence interval 1.9-6.0), and lens opacity (relative risk = 2.4, 95% confidence interval 1.6-3.8). CONCLUSIONS The findings from this population-based cohort confirm the predictive power of microalbuminuria as a risk factor for mortality in NIDDM. In contrast to prospective studies of conventional cardiovascular risk factors in NIDDM, consistent evidence indicates that microalbuminuria is an independent predictor of excess mortality regardless of the collection procedure used.