CONTEXT: Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants. OBJECTIVE: To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women. DATA SOURCES AND STUDY SELECTION: A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included. DATA EXTRACTION: Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF (< 7.9 METs), intermediate CRF (7.9-10.8 METs), or high CRF (> or = 10.9 METs). CHD and CVD were combined into 1 outcome (CHD/CVD). Risk ratios (RRs) for a 1-MET higher level of MAC and for participants with lower vs higher CRF were calculated with a random-effects model. DATA SYNTHESIS: Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P < .001) and for CHD/CVD events of 1.56 (95% CI, 1.39-1.75; P < .001), adjusting for heterogeneity of study design. Compared with participants with intermediate CRF, those with low CRF had an RR for all-cause mortality of 1.40 (95% CI, 1.32-1.48; P < .001) and for CHD/CVD events of 1.47 (95% CI, 1.35-1.61; P < .001), adjusting for heterogeneity of study design. CONCLUSIONS: Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with a MAC of less 7.9 METs.