CONTEXT: The association of triglycerides with incident cardiovascular disease remains controversial. Although triglyceride levels are typically obtained in the fasting state, postprandial hypertriglyceridemia may play an important role in atherosclerosis. OBJECTIVE: To determine the association of triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 26,509 initially healthy US women (20,118 fasting and 6391 nonfasting) participating in the Women’s Health Study, enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years. Triglyceride levels were measured in blood samples obtained at time of enrollment. MAIN OUTCOME MEASURE: Hazard ratios for incident cardiovascular events (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization, or cardiovascular death). RESULTS: At baseline, triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance. During a median follow-up of 11.4 years, 1001 participants experienced an incident cardiovascular event (including 276 nonfatal myocardial infarctions, 265 ischemic strokes, 628 coronary revascularizations, and 163 cardiovascular deaths), for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up. After adjusting for age, blood pressure, smoking, and use of hormone therapy, both fasting and nonfasting triglyceride levels predicted cardiovascular events. Among fasting participants, further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association (fully adjusted hazard ratio [95% confidence interval] for increasing tertiles of triglyceride levels: 1 [reference], 1.21 [0.96-1.52], and 1.09 [0.85-1.41] [P = .90 for trend]). In contrast, nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models (hazard ratio [95% confidence interval] for increasing tertiles of levels: 1 [reference], 1.44 [0.90-2.29], and 1.98 [1.21-3.25] [P = .006 for trend]). In secondary analyses stratified by time since participants‘ last meal, triglyceride levels measured 2 to 4 hours postprandially had the strongest association with cardiovascular events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P<.001 for trend]), and this association progressively decreased with longer periods of fasting. CONCLUSIONS: In this cohort of initially healthy women, nonfasting triglyceride levels were associated with incident cardiovascular events, independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels showed little independent relationship.