ABSTRACT: Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus. Few studies have tested for a relationship with coronary heart disease (CHD) or intermediate biomarkers. The role of artificially sweetened beverages is also unclear.We performed an analysis of the Health Professionals Follow-Up Study, a prospective cohort study including 42 883 men. Associations of cumulatively averaged sugar-sweetened (eg, sodas) and artificially sweetened (eg, diet sodas) beverage intake with incident fatal and nonfatal CHD (myocardial infarction) were examined with proportional hazard models. There were 3683 CHD cases over 22 years of follow-up. Participants in the top quartile of sugar-sweetened beverage intake had a 20% higher relative risk of CHD than those in the bottom quartile (relative risk=1.20; 95% confidence interval, 1.09-1.33; P for trend <0.01) after adjustment for age, smoking, physical activity, alcohol, multivitamins, family history, diet quality, energy intake, body mass index, pre-enrollment weight change, and dieting. Artificially sweetened beverage consumption was not significantly associated with CHD (multivariate relative risk=1.02; 95% confidence interval, 0.93-1.12; P for trend=0.28). Adjustment for self-reported high cholesterol, high triglycerides, high blood pressure, and diagnosed type 2 diabetes mellitus slightly attenuated these associations. Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides, C-reactive protein, interleukin-6, and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein, lipoprotein(a), and leptin (P<0.02).Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids, inflammatory factors, and leptin. Artificially sweetened beverage intake was not associated with CHD risk or biomarkers.