Background: Severe traumatic brain injury (TBI) is associated with paroxysmal sympathetic hyperactivity (PSH), which is characterized by catecholamine surge. β-blockers can break this cycle by protecting β-receptor rich brain cells to decrease the cerebral oxygen demand, which may attenuate cerebral ischemia and secondary brain injury. In addition, β-blockers are beneficial to decrease hypermetabolism, lighten cardiac workload and ischemia, and lessen cerebral oxygen demand in head injury. Objective: The purpose of the study was to evaluate the effect of beta blockers (propranolol) on patients with acute TBI. Patients and methods: A total of 400 patients who were presented and admitted to Mansoura University Emergency Hospital (MUEH) surgical ICU with TBI were enrolled in this study. The enrolled patients were divided equally and randomly into 2 groups: Propranolol group (200 patients) who received IV propranolol and control group (200 patients) who received the standard medical and surgical care without propranolol. Results: The clinical outcome of the studied cases were obviously better in propranolol group (P <0.05). The neurologic examination; according to GCS; was improved in 34% vs. 27.5%. The cardiac examination; according to ECG showed changes in 12% vs. 26.5% in propranolol and control groups respectively. Also, the secondary outcome assessment parameters including ICU length of stay (LOS), ward LOS, mechanical ventilation, ventilation periods, survival rate and unfavorable GOS were better in propranolol group (P <0.05). Conclusion: Early propranolol administration is associated with post-head injury cardioprotective and neuroprotective effects, lower hospital resources use and better functional outcome.