BACKGROUND: To better understand the role of acute normovolemic hemodilution (ANH) in a surgical setting with high risk of bleeding, we analyzed all randomized controlled trials (RCTs) in the setting of cardiac surgery that compared ANH with standard intraoperative care. The aim was to assess the incidence of ANH-related number of allogeneic red blood cell units (RBCu) transfused. Secondary outcomes included the rate of allogeneic blood transfusion and estimated total blood loss. METHODS: Twenty-nine RCTs for a total of 2439 patients (1252 patients in the ANH group and 1187 in the control group) were included in our meta-analysis using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE. RESULTS: Patients in the ANH group received fewer allogeneic RBCu transfusions (mean difference = -0.79; 95% confidence interval [CI], -1.25 to -0.34; P = .001; I = 95.1%). Patients in the ANH group were overall transfused less with allogeneic blood when compared with controls (356/845 [42.1%] in the ANH group versus 491/876 [56.1%] in controls; risk ratio = 0.74; 95% CI, 0.62 to 0.87; P <.0001; I = 72.5%), and they experienced less postoperative blood loss (388 mL in ANH versus 450 mL in control; mean difference = -0.64; 95% CI, -0.97 to -0.31; P <.0001; I = 91.8%). CONCLUSIONS: ANH reduces the number of allogeneic RBCu transfused in the cardiac surgery setting together with a reduction in the rate of patients transfused with allogeneic blood and with a reduction of bleeding.