Context: Coronary heart disease (CHD) is responsible for about 15% of all deaths worldwide and is identified as a top priority for decision makers. Both primary and secondary prevention are considered key strategies in the prevention of CHD. The aim of this study was to assess the efficacy of nonpharmacologic interventions with multiple lifestyle components in patients with established CHD in comparison to usual care. For this reason, a systematic review and meta-analysis of RCTs were performed. Evidence acquisition: The Cochrane Library, MEDLINE, and EMBASE databases were examined until March 31, 2012 (without start date) in order to identify studies addressing patient-tailored multifactorial lifestyle interventions aimed at reducing more than one cardiovascular risk factor in patients with established CHD. Primary endpoints were fatal and nonfatal cardiovascular events. Secondary outcomes were overall mortality and cardiovascular disease-associated hospital readmissions. Evidence synthesis: The search strategy yielded 14 unique RCTs, which were considered in the qualitative analysis. Nine of them contributed to the meta-analysis. A random effects model was used to pool the data. The meta-analysis showed a significant risk reduction of 18% (relative risk 0.82, 95% CI=0.69, 0.98) of fatal cardiovascular events in patients undergoing multifactorial lifestyle interventions. Further, a nonsignificant reduction of nonfatal events, overall mortality and hospital readmissions was found. Conclusions: Multifactorial lifestyle interventions aimed at improving modifiable risk factors in patients with established CHD reduce the risk for fatal cardiovascular events. Therefore, they may have added value in secondary prevention of CHD.