To examine the sex-specific contributions of the metabolic syndrome and microalbuminuria to cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in community-dwelling older adults, 869 women and 575 men aged 40 to 96 years (mean age 71) completed questionnaires, physical examinations, and fasting laboratory tests between 1992 and 1995. Participants were followed over an average of 8 years. CVD and CHD mortality were analyzed using Cox proportional hazards models. At baseline, 267 participants had the Adult Treatment Panel III metabolic syndrome, 151 had microalbuminuria, and 34 had both. During follow-up, there were 180 CVD deaths, including 83 CHD deaths. In women, microalbuminuria was associated with a twofold increased risk of CVD and CHD mortality (p<or=0.01). Women with both microalbuminuria and the metabolic syndrome (n=18) had a threefold increased risk of CVD mortality and a fivefold increased risk of CHD mortality compared with women without either (n=657). A significant interaction existed between microalbuminuria and the metabolic syndrome in the prediction of both CVD and CHD (p=0.02). In men, neither the combination of the metabolic syndrome and microalbuminuria (n=16), nor either alone, significantly increased the risk of CVD or CHD mortality. In conclusion, in this cohort, microalbuminuria and the metabolic syndrome together were a more powerful predictor of CVD mortality than either alone in women but not in men. Screening for microalbuminuria in older women may identify women at high risk for CVD mortality beyond that conferred by risk factors included in the metabolic syndrome.