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Object: To evaluate the outcome of patients undergoing a decompressive craniectomy (DC) in traumatic brain injury (TBI) and the factors predicting outcome. Materials and Methods: A total of 1,236 patients with TBI operated with a DC from January 2008 to December 2013 at a tertiary care hospital were included in the study. The data from the hospital computerized database was retrospectively analyzed and 324 (45%) patients were followed-up for a mean duration of 25.3 months (range 3-42 months) among the cohort of 720 alive patients. The institute's ethical committee clearance was obtained before the start of the study. Results: There were 81% males with a median age [interquartile range (IQR)] of 32 (23-45) years. The mortality rate and median (IQR) Glasgow outcome score (GOS) at discharge in patients presenting with minor, moderate, and severe head injury were 18%, 5 (4-5); 28%, 4 (1-5); and 47.4%, 2 (1-4), respectively. An overall favorable outcome (GOS 4 and 5) at discharge was observed in 46.5% patients and in 39% patients who presented with severe TBI. Only 7.5% patients were in a persistent vegetative state (PVS), while 78% had an overall favorable outcome at the last follow-up of surviving patients (P < 0.001). On multivariate analysis, the factors predictive of a favorable GOS at discharge were: a younger age (odds ratio (OR) 1.03, confidence interval (CI) = 1.02-1.04; P < 0.001), no pupillary abnormalities at admission (OR 2.28, CI = 1.72-3.02; P < 0.001), absence of preoperative hypotension (OR 1.91, CI = 1.08-3.38; P = 0.02), an isolated TBI (OR 1.42, CI = 1.08-1.86; P = 0.01), absence of a preoperative infarct (OR 3.68, CI = 1.74-7.81; P = 0.001), presence of a minor head injury (OR 6.33, CI = 4.07-9.86; P < 0.001), performing a duraplasty (OR 1.86, CI = 1.20-2.87; P = 0.005) rather than a slit durotomy (OR 3.95, CI = 1.67-9.35; P = 0.002), and, avoidance of a contralateral DC (OR 3.58, CI = 1.90-6.73; P < 0.001). Conclusions: The severity of head injury, performing a duraplasty rather than a slit durotomy, avoidance of a contralateral DC, and the presence of preoperative hypotension, infarct, and/or pupillary asymmetry have the highest odds of predicting the short term GOS at the time of discharge, after a DC in patients with TBI. Although DC carries a high risk of mortality, the probability of the survivors having a favorable outcome is signiicantly more as compared to those who remain in a PVS. [ABSTRACT FROM AUTHOR]