We performed a prospective observational study on 6,602 subjects (94% for 5 years and 34% for 10 to 15 years) who underwent coronary artery bypass graft surgery (CABG) between 1982 and 1992. We examined whether triglyceride concentrations adjusted for other factors (total cholesterol, history of diabetes mellitus, systemic hypertension, left ventricular function, number of coronary arteries significantly narrowed, and use of the internal thoracic arteries) explained total and event-free survival. These analyses were duplicated within gender (1,354 women and 5,248 men). This approach allowed a determination of any gender-related disparities in lipid predictors. Triglycerides in the highest quartile were associated with an increased risk of mortality of 20% (confidence interval [CI] 1.0 to 1.4). Similar risk was seen for event-free survival. Although there was no evidence of gender differences in adjusted survival (p = 0.33), a gender by triglyceride interaction (p = 0.004) indicated that the response to high triglycerides as related to survival did differ by gender. Specifically, women had a dramatically higher risk (hazard ratio [HR] 1.5, CI 1.1 to 2.1) than men (HR 1.1, CI 0.9 to 1.3). Both men and women did have triglyceride-associated risk with regard to event-free survival (HR in men 1.2, CI 1.1 to 1.4; HR in women 1.4, CI 1.1 to 1.8). Examination of high-density lipoprotein cholesterol in a subcohort did not eliminate the observed triglyceride effects. Thus, triglyceride baseline values are primary determinants (similar to baseline left ventricular function or extent of coronary disease) for long-term total and event-free mortality after CABG in women but not in men.