Cardiopulmonary bypass is associated with significant morbidities, and the ideal temperature management during cardiopulmonary bypass remains uncertain. This review assessed the benefits and risks of maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery. A total of 6731 patients from 44 randomized controlled trials in 14 countries, comparing normothermic (>34°C) and hypothermic (≤34°C) cardiopulmonary bypass in cardiac surgery (>18 years of age), were identified from MEDLINE (1966 to August 10, 2009), EMBASE (1988 to August 10, 2009), and Cochrane controlled trials register and subject to meta-analysis. Two investigators examined all studies and extracted the data independently. Mortality after normothermic and hypothermic bypass was not significantly different (1.4% vs. 1.9% respectively, relative risk [RR] 1.38, 95% confidence interval [CI] 0.94–2.04, I2= 0%, P= 0.10). Hypothermic bypass was, however, associated with an increased risk of allogeneic red blood cells (RR 1.19, 95% CI 1.07–1.34, I2= 0%, P= 0.002), fresh frozen plasma (RR 1.54, 95% CI 1.06–2.24, I2= 7.7%, P= 0.02), and platelet transfusion (RR 2.53, 95% CI 1.26–5.06, I2= 44%, P= 0.009). The risk of stroke, cognitive decline, atrial fibrillation, use of inotropic support or intra-aortic balloon pump, myocardial infarction, all-cause infections, and acute kidney injury after cardiac surgery was not significantly different between the two groups. The differences in the bypass time and targeted perfusion temperature were not significantly related to the risk of mortality and stroke. The current evidence suggests that maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery is as safe as that of hypothermic surgery, and associated with a reduced risk of allogeneic blood transfusion.