Introduction: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is one of the promising candidates, with an acceptable diagnostic value for predicting head computed tomography (CT) scan findings. However, there has been a controversy between studies and still, there is no general overview on this. Therefore, the current systematic review and meta-analysis attempted to estimate the value of UCH-L1 in predicting intracranial lesions in traumatic brain injury.Methods: Two independent reviewers screened records from the search of four databases Medline, Embase, Scopus and Web of Science. The data were analyzed in the STATA 14.0 statistical program and the findings were reported as a standardized mean difference (SMD), summary receiver performance characteristics curve (SROC), sensitivity, specificity, and diagnostic odds ratio with 95% confidence interval (95% CI).Results: Finally, the data of 13 articles were entered into the meta-analysis. The mean serum level of UCH-L1 was significantly higher in patients with CT-positive than in TBI patients with CT negative (SMD = 1.67, 95% CI: 1.12 to 2.23, I2 = 98.1%; p <0.0001). The area under the SROC curve for UCH-L1 in the prediction of intracranial lesions after mild TBI was 0.83 (95% CI: 0.80 to 0.86). Sensitivity, specificity and diagnostic odds ratio of serum UCH-L1 was 0.97 (95% CI: 0.92 to 0.99), 0.40 (95% CI: 0.30 to 0.51) and 19.37 (95% CI: 7.25 to 51.75), respectively. When the analysis was limited to assessing the serum level of UCH-L1 within the first 6 hours after mild TBI, its sensitivity and specificity increased to 0.99 (95% CI: 0.94 to 1.0) and 0.44 (95% CI: 0.38 to 0.052), respectively. In addition, the diagnostic odds ratio of 6-hour serum level of UCH-L1 in the prediction of intracranial lesions was 680.87 (95% CI: 50.50 to 9197.97).Conclusion: Moderate level of evidence suggests that serum/plasma levels of UCH-L1 have good value in prediction of head CT findings. It was also found that evaluation of serum/plasma level of UCH-L1 within the first 6 hours following TBI would increase its predictive value. However, there is a controversy about the best cutoffs of the UCH-L1
