BACKGROUND: The combined effect of modifiable health factors on the risk of cardiovascular disease (CVD) mortality has not been well established. The objective of this study was to determine the association between 5 modifiable health factors in combination on the risk of CVD mortality in a sample of adult men. METHODS: A cohort of 38,110 men (aged 20-84 years and of middle and upper socioeconomic strata) was followed over time until their date of death or December 31, 2003. A health profile score (unweighted and weighted) was developed based on cardiorespiratory fitness (CRF; moderate or high vs low), self-reported physical activity (active vs inactive), smoking status (not current vs current), alcohol consumption (1-14 drinks per week vs 0 or >14 drinks per week), and body mass index (BMI; 18.5-24.9 vs >or=25.0 kg/m(2)). RESULTS: During 16.1 +/- 8.4 years of follow-up and 613,571 man-years of exposure, there were 949 deaths from CVD. High CRF, normal BMI, being physically active, and not currently smoking were individually associated with reduced risk of CVD mortality after adjusting for confounders. When considered in combination, a minimum of 2 of 5 positive health factors reduced the risk of CVD mortality (hazard ratio = 0.67, 95% CI 0.49-0.91). The weighted score indicated that a combination of high CRF, not currently smoking, and normal BMI is of most clinical importance to CVD mortality (hazard ratio = 0.31, 95% CI 0.24-0.39). CONCLUSIONS: Exposure to increasing numbers of beneficial health factors in adulthood reduced the risk of CVD mortality in men, and multibehavioral prevention efforts in adulthood should be encouraged.