PURPOSE: Although evidence from observational studies in a variety of clinical settings supports the utility of cerebral oximetry as a predictor of outcomes, prospective clinical trials thus far have reported conflicting results. This systematic review and meta-analysis was designed to evaluate the influence of management associated with intraoperative cerebral oximetry on postoperative outcomes. The primary outcome was postoperative cognitive dysfunction (POCD), with secondary outcomes that included postoperative delirium, length of intensive care unit (ICU) stay, and hospital length of stay (LOS). SOURCE: After searching the PubMed, EMBASE, Cochrane Library, Scopus, and Google Scholar databases, all randomized controlled trials (RCTs) assessing the impact of intraoperative cerebral oximetry-guided management on clinical outcomes following surgery were identified. PRINCIPAL FINDINGS: Fifteen RCTs comprising 2,057 patients (1,018 in the intervention group and 1,039 in control group) were included. Intraoperative management guided by the use of cerebral oximetry was associated with a reduction in the incidence of POCD (risk ratio [RR] 0.54; 95% confidence interval [CI], 0.33 to 0.90; P = 0.02; I2 = 85%) and a significantly shorter length of ICU stay (standardized mean difference [SMD], -0.21 hr; 95% CI, -0.37 to -0.05; P = 0.009; I2 = 48%). In addition, overall hospital LOS (SMD, -0.06 days; 95% CI, -0.18 to 0.06; P = 0.29; I2 = 0%) and incidence of postoperative delirium (RR, 0.69; 95% CI, 0.36 to 1.32; P = 0.27; I2 = 0%) were not impacted by the use of intraoperative cerebral oximetry. CONCLUSIONS: Intraoperative cerebral oximetry appears to be associated with a reduction in POCD, although this result should be interpreted with caution given the significant heterogeneity in the studies examined. Further large (ideally multicentre) RCTs are needed to clarify whether POCD can be favourably impacted by the use of cerebral oximetry-guided management.