Résumé : Traumatic brain injury (TBI) is a major public health burden, causing death and disability worldwide. Intracranial hypertension and brain hypoxia are the main mechanisms of secondary brain injury. As such, management strategies guided by intracranial pressure (ICP) and brain oxygen (PbtO2) monitoring could improve the prognosis of these patients. Our objective was to summarize the current evidence regarding the impact of PbtO2-guided therapy on the outcome of patients with TBI. We performed a systematic search of PubMed, Scopus, and the Cochrane library databases, following the protocol registered in PROSPERO. Only studies comparing PbtO2/ICP–guided therapy with ICP-guided therapy were selected. Primary outcome was neurological outcome at 3 and 6 months assessed by using the Glasgow Outcome Scale; secondary outcomes included hospital and long-term mortality, burden of intracranial hypertension, and brain tissue hypoxia. Out of 6254 retrieved studies, 15 studies (n = 37,245 patients, of who 2184 received PbtO2-guided therapy) were included in the final analysis. When compared with ICP-guided therapy, the use of combined PbO2/ICP–guided therapy was associated with a higher probability of favorable neurological outcome (odds ratio 2.21 [95% confidence interval 1.72–2.84]) and of hospital survival (odds ratio 1.15 [95% confidence interval 1.04–1.28]). The heterogeneity (I2) of the studies in each analysis was below 40%. However, the quality of evidence was overall low to moderate. In this meta-analysis, PbtO2-guided therapy was associated with reduced mortality and more favorable neurological outcome in patients with TBI. The low-quality evidence underlines the need for the results from ongoing phase III randomized trials.