Sex hormone-binding globulin (SHBG) has been shown to be associated with several cardiovascular disease (CVD) risk factors. We examined the prospective association between SHBG and the risk of CVD and ischemic heart disease (IHD) death in 760 men and 624 women, aged 50-82 yr, who were free of heart disease at baseline. Health status and cause of death were determined annually for 99.9% of the cohort for 19 yr. SHBG correlated negatively with body mass index in both sexes and increased with age in men. After adjusting for age and body mass index, SHBG correlated negatively with fasting plasma glucose in men and women and with total cholesterol and triglycerides in men. There were 235 CVD and 134 IHD deaths in men and 153 CVD and 80 IHD deaths in women over the 19-yr follow-up. The quintile of baseline SHBG was unrelated to CVD or IHD mortality rate. No association was found in sex-specific, multiply-adjusted Cox proportional hazard models. All risk ratios were close to 1, and 95% confidence intervals were narrow and included 1. Although associated with several strong heart disease risk factors, the SHBG level does not predict CVD or IHD mortality in men or women.