BACKGROUND High-level evidence concerning the restoration of endodontically treated posterior teeth by means of direct composite resin or indirect restorations is lacking. OBJECTIVE The purpose of this systematic review and meta-analysis was to analyze the current literature on the direct and indirect restoration of endodontically treated posterior teeth. METHODS Databases MEDLINE, CENTRAL, and EMBASE were screened. Risk of bias was assessed by using the ROB2 tool for RCTs and the ROBINS-I tool for prospective and retrospective clinical studies. Randomized clinical trials (RCTs) and prospective and retrospective studies comparing direct composite resin and indirect restorations on endodontically treated posterior teeth were included. Outcomes were tooth and restoration survival. A meta-analysis was conducted for tooth retention and restorative success. RESULTS Twenty-two studies were included (2 RCTs, 3 prospective, and 17 retrospective). Over the short term (2.5 to 3 years), low-quality evidence suggested no difference in tooth survival. For the prospective and retrospective clinical trials, the overall risk of bias was serious to critical from the risk of confounding because of a difference in restorative indication: Direct restorations were fabricated when one marginal ridge remained or when tooth prognosis was unfavorable. For short-term restorative success, low-quality evidence suggested no difference between the direct and indirect restorations. CONCLUSIONS For the short term (2.5 to 3 years), low-quality evidence suggests no difference in tooth survival or restoration quality. To assess the influence of the type of restoration on the survival and restorative success of endodontically treated posterior teeth, clinical trials that control for the amount of coronal tooth tissue and other baseline characteristics are needed.