OBJECTIVE To examine the association of hyperglycemia, as measured by GHb, with subsequent mortality in a nationally representative sample of adults. RESEARCH DESIGN AND METHODS We included adults aged > or =20 years who participated in Third National Health and Nutrition Examination Survey (1988-1994) and had complete information, including baseline diabetes status by self-report and measured GHb (n = 19,025) and follow-up through the end of 2000 for mortality. RESULTS In the overall population, higher levels of GHb were associated with increased risk of mortality from all causes, heart disease, and cancer. After adjustment for potential risk factors, the relative hazard (RH) for adults with GHb > or =8% compared with adults with GHb <6% was 2.59 (95% CI 1.88-3.56) for all-cause mortality, 3.38 (1.98-5.77) for heart disease mortality, and 2.64 (1.17-5.97) for cancer mortality. Among adults with diagnosed diabetes, having GHb > or =8% compared with GHb <6% was associated with higher all-cause mortality (RH 1.68, 95% CI 1.03-2.74) and heart disease mortality (2.48, 1.09-5.64), but there was no increased risk of cancer mortality by GHb category. Among adults without diagnosed diabetes, there was no significant association of all-cause, heart disease, or cancer mortality and GHb category. CONCLUSIONS These results highlight the importance of GHb levels in mortality risk among a nationally representative sample of adults with and without diagnosed diabetes and indicate that higher levels are associated with increased mortality in adults with diabetes.