Prospective data relating cardiorespiratory fitness (CRF) with nonfatal cardiovascular disease (CVD) events are limited to studies in men or studies of combined fatal and nonfatal CVD endpoints. The authors examined the association between CRF and nonfatal CVD events in 20,728 men and 5,909 women without CVD at baseline. All participants performed a maximal treadmill exercise test and completed a follow-up health survey in the Aerobics Center Longitudinal Study (Dallas, Texas) between 1971 and 2004. There were 1,512 events in men and 159 events in women during an average follow-up of 10 years. Across incremental CRF groups, age- and examination year-adjusted event rates per 10,000 person-years were 107.9, 75.2, and 50.3 in men (p(trend) < 0.001) and 41.9, 27.7, and 20.8 in women (p(trend) = 0.002). After further adjustment for smoking, alcohol intake, family history of CVD, and abnormal exercise electrocardiogram responses, hazard ratios were 1.00 (referent), 0.82 (95% confidence interval (CI): 0.72, 0.94), and 0.61 (95% CI: 0.53, 0.71) in men, p(trend) < 0.001, and were 1.00 (referent), 0.74 (95% CI: 0.49, 1.13), and 0.63 (95% CI: 0.40, 0.98) in women, p(trend) = 0.05. After adjustment for other CVD predictors, the association remained significant in men but not in women.