PURPOSE: The objective of this study is to prospectively examine the independent and joint effects of alcohol consumption and cardiorespiratory fitness on the incidence of metabolic syndrome (MetS) in a cohort of men. Methods: A prospective examination was done of 3411 apparently healthy men at baseline, who came to the Cooper Clinic (Dallas, TX) for at least two preventive visits (1979-2010). Primary exposure variables were cardiorespiratory fitness and alcohol intake; the outcome measure was MetS and the components thereof. Cox proportional hazards models were computed to assess the relation between the exposure variables and the incidence of MetS while adjusting for confounders. Results: For a mean follow-up period of 9 yr (SD = 7.8), 276 men developed MetS. In multivariable analysis, a dose-response relationship was observed between increased levels of fitness and reduced MetS risk (moderate fitness: HR = 0.60; 95% confidence interval (CI), 0.43-0.82; high fitness: HR = 0.49, 95% CI, 0.35-0.69). When examining the independent effects of alcohol, light drinking increased the risk for MetS by 66% (HR = 1.66, 95% CI, 1.11-2.48). No statistically significant interaction effect was observed between alcohol and fitness in relation to MetS (P = 0.32). When assessing the relation between each exposure and the components of MetS, higher fitness consistently reduced the risk of all components, whereas lower alcohol intake reduced the risk of elevated glucose and blood pressure and increased the risk for low HDL cholesterol. ConclusionS: Among this cohort of men, higher fitness levels reduced the risk for MetS and its components. The relation between alcohol intake levels and metabolic risk was more complex and not reflected when examining MetS as a whole. Copyright © 2012 by the American College of Sports Medicine.