Context: Current guidelines recommend exercise for optimal cardiovascular health, although evidence from intervention trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. Objective: To perform a meta-analysis of randomized controlled trials (RCTs) to quantify the impact of exercise training on cardiorespiratory fitness (CRF) and a variety of standard and novel biomarkers for cardio-metabolic health in adults without cardiovascular disease (CVD). Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1965 to March 2014. Study Selection: Two investigators (X. Lin and X. Zhang) selected 159 RCTs (7,282 participants) that evaluated the effects of exercise interventions on CRF and circulating CVD biomarkers. Data Extraction: Data were extracted by two researchers using a standardized protocol. Data Synthesis: In the primary analysis, DerSimonian and Laird random-effect models were used to compute weighted mean differences (WMDs) and 95% confidence intervals (95% CIs) comparing exercise groups to control groups. In addition, effect modifications were examined using meta-regression and subgroup analyses stratified by pre-specified potential modifiers, including age, sex, body mass index, lifestyle, health status, and trial duration. Exercise training significantly improved CRF, lipid and lipoprotein metabolism, glucose intolerance and insulin resistance, systematic inflammation, and hemostasis. (Table) We also found that exercise effects were modified by age, sex, and health status such that people under 50 years, men, and people with type 2 diabetes, hypertension, hyperlipidemia, or metabolic syndrome appeared to benefit more from exercise interventions. Conclusion: This meta-analysis indicates that exercise training significantly improved CRF and some biomarkers of cardio-metabolic health. Significant effect modifications were also identified by age, sex, and health status. (Table Presented).