Objectives Goal-directed optimisation of cerebral oxygenation using near-infrared spectroscopy (NIRS) during cardiopulmonary bypass is widely used. We tested the hypotheses that the use of NIRS cerebral oximetry results in reductions in cerebral injury (neurocognitive function, serum biomarkers), injury to other organs including the heart and brain, transfusion rates, mortality and resource use. Design Systematic review and meta-analysis. Setting Tertiary cardiac surgery centres in North America, Europe and Asia. Participants A search of Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature Plus from inception to November 2016 identified 10 randomised trials, enrolling a total of 1466 patients, all in adult cardiac surgery. Interventions NIRS-based algorithms designed to optimise cerebral oxygenation versus standard care (non-NIRS-based) protocols in cardiac surgery patients during cardiopulmonary bypass. Outcome measures Mortality, organ injury affecting the brain, heart and kidneys, red cell transfusion and resource use. Results Two of the 10 trials identified in the literature search were considered at low risk of bias. Random-effects meta-analysis demonstrated similar mortality (risk ratio (RR) 0.76, 95% CI 0.30 to 1.96), major morbidity including stroke (RR 1. 08, 95% CI 0.40 to 2.91), red cell transfusion and resource use in NIRS-treated patients and controls, with little or no heterogeneity. Grades of Recommendation, Assessment, Development and Evaluation of the quality of the evidence was low or very low for all of the outcomes assessed. Conclusions The results of this systematic review did not support the hypotheses that cerebral NIRS-based algorithms have clinical benefits in cardiac surgery