Guidelines support the use of a restrictive strategy in blood transfusion management in a variety of clinical settings. However, recent randomized controlled trials (RCTs) performed in the perioperative setting suggest a beneficial effect on survival of a liberal strategy. We aimed to assess the effect of liberal and restrictive blood transfusion strategies on mortality in perioperative and critically ill adult patients through a meta-analysis of RCTs. We searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, Transfusion Evidence Library, and Google Scholar up to 27 March 2015, for RCTs performed in perioperative or critically ill adult patients, receiving a restrictive or liberal transfusion strategy, and reporting all-cause mortality. We used a fixed or random-effects model to calculate the odds ratio (OR) and 95% confidence interval (CI) for pooled data. We assessed heterogeneity using Cochrane's Q and I2 tests. The primary outcome was all-cause mortality within 90-day follow-up. Patients in the perioperative period receiving a liberal transfusion strategy had lower all-cause mortality when compared with patients allocated to receive a restrictive transfusion strategy (OR 0.81; 95% CI 0.66−1.00; P=0.05; I2=25%; Number needed to treat=97) with 7552 patients randomized in 17 trials. There was no difference in mortality among critically ill patients receiving a liberal transfusion strategy when compared with the restrictive transfusion strategy (OR 1.10; 95% CI 0.99−1.23; P=0.07; I2=34%) with 3469 patients randomized in 10 trials. According to randomized published evidence, perioperative adult patients have an improved survival when receiving a liberal blood transfusion strategy.