Previous studies have evaluated the strength of the association between traditional risk factors and cardiovascular disease (CVD) across varying lengths of follow-up in men. However, to our knowledge, little is known regarding the behavior of these risk factors across time in women. Thus, we sought to determine the association between traditional risk factors in men and women across follow-up periods of 0 to 10, 10 to 20, and >20 years. We studied 9,033 men and 7,575 women (ages 40 to 59 years) from 1967 to 1973 from the Chicago Heart Association Detection Project in Industry. Multivariable-adjusted Cox proportional hazard models were constructed to compare the hazard ratios (HRs) and 95% confidence intervals (CI) for CVD risk factors measured at baseline across different periods of follow-up (0 to 10, 10 to 20, and >20 years). In women, the HRs for smoking and diabetes mellitus were strongest at 0 to 10 years (HR 5.38, 95% CI 2.99 to 9.67 and 3.84, 95% CI 1.82 to 8.13, respectively) but decreased at >20 years (HR 1.71, 95% CI 1.48 to 1.97 and 1.60, 95% CI 1.10 to 2.32, respectively). In men, the HR (per 4 kg/m(2)) for body mass index appeared to increase (0 to 10 years, 1.01, 95% CI 0.90 to 1.14; >20 years, 1.20, 95% CI 1.13 to 1.28). In women, the association was similar across all follow-up periods. For both men and women, the HR for total serum cholesterol remained unchanged across the follow-up. In conclusion, we found gender differences in the patterns of association between risk factors measured at baseline and CVD death across different periods of follow-up. In women, the increased risk associated with both diabetes mellitus and smoking was most prominent in the early follow-up periods.