OBJECTIVE Traumatic brain injury is a major cause of death and disability, yet many predictors of outcome are not precise enough to guide initial clinical decision-making. Although increasingly used in the early phase following traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus undertook a systematic review and meta-analysis of studies evaluating the predictive value of acute MRI lesion patterns for discriminating clinical outcome in traumatic brain injury. METHODS MEDLINE, EMBASE, BIOSIS, and CENTRAL from inception to November 2015. METHODS Studies of adults who had MRI in the acute phase following moderate or severe traumatic brain injury. Our primary outcomes were all-cause mortality and the Glasgow Outcome Scale. METHODS Two authors independently performed study selection and data extraction. We calculated pooled effect estimates with a random effects model, evaluated the risk of bias using a modified version of Quality in Prognostic Studies and determined the strength of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS We included 58 eligible studies, of which 27 (n = 1,652) contributed data to meta-analysis. Brainstem lesions were associated with all-cause mortality (risk ratio, 1.78; 95% CI, 1.01-3.15; I = 43%) and unfavorable Glasgow Outcome Scale (risk ratio, 2.49; 95% CI, 1.72-3.58; I = 81%) at greater than or equal to 6 months. Diffuse axonal injury patterns were associated with an increased risk of unfavorable Glasgow Outcome Scale (risk ratio, 2.46; 95% CI, 1.06-5.69; I = 74%). MRI scores based on lesion depth demonstrated increasing risk of unfavorable neurologic outcome as more caudal structures were affected. Most studies were at high risk of methodological bias. CONCLUSIONS MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with long-term survival and neurologic outcome. Given the high risk of bias in the current body of literature, large well-controlled studies are necessary to better quantify the prognostic role of early MRI in moderate and severe traumatic brain injury.