Background Traumatic brain injury (TBI) is responsible for up to 30% of all injury-related deaths. The majority of patients with severe TBI require mechanical ventilation (MV). To date, no pharmacologic agent has been developed to improve outcomes in TBI. The primary aim of this prospective study was to investigate whether early use of low-dose propranolol within 24 h in patients with severe TBI can affect their weaning from MV or not. Patients and methods This study was carried out on 340 adult patients with severe TBI randomly assigned to two groups. The early propranolol after traumatic brain injury (EPAT) group (102) received propranolol 40 mg twice daily within 24 h from admission. The non-EPAT group (238) did not receive any β blockers. Results EPAT patients showed lower duration of MV (7.74 vs. 11.14 days, P=0.0013). The length of stay in ICU was lower in the EPAT group (10.62 vs. 14.13 days, P=0.003), but there was no statistically significant difference in mortality between the two groups studied (P=0.392). Conclusion Early use of propranolol does not increase episodes of bradycardia or hypotension. Early propranolol after TBI can be used safely and may be associated with decreased days on MV and ICU length of stay.