Background: Traumatic brain injury (TBI) is a worldwide major and challenging public health problem responsible for 39% global mortality. TBI is considered one of the leading causes of death in pediatrics and adults less than 45 years. This study aimed to primarily evaluate the outcome of decompressive craniectomy (DC) in TBI and secondly to assess the factors that may predict the outcome of DC in those patients. Methods: This prospective cohort study was conducted on 30 patients with TBI with increased intracranial pressure not responding to medical treatment. All studied cases underwent neurological examination, radiological and laboratory investigations. Results: Regarding the factors associated with poor outcome, in the univariate analysis, it was found that older age, female gender, the lower the Glasgow coma scale (GCS) at admission, the longer duration between injury and operation, the more midline shift, presence of associated clinical features and bilaterality of DC . Those factors were significantly associated with poor outcome (death or severe disability), with p-values of 0.02, 0.03, 0.002, 0.02, 0.03, 0.01 and 0.04, respectively. In the multivariate analysis, only lower GCS, longer duration from injury and operation and bilaterality of DC were significant predictors associated with poor neurological outcome. Conclusion: We observed a high mortality rate of 46.7%. Factors such as old age, lower GCS at admission, longer time from injury to surgery, presence of bilateral unreactive pupils, associated injuries, and female gender were associated with poor outcomes. While midline shift improved postoperatively, complications such as residual subdural hematoma and wound infections were common.