Objectives: We aimed to investigate the use of sedation in patients with severe traumatic brain injury (TBI), focusing on the choice of sedative agent, dose, duration, and their association with clinical outcomes. Design: Multinational, multicentre, retrospective observational study. Settings: 14 trauma centres in Europe, Australia and the United Kingdom. Participants: A total of 262 adult patients with severe TBI and intracranial pressure monitoring. Main outcome measures: We described how sedative agents were used in this population. The primary outcome was 60-day mortality according to the use of different sedative agents. Secondary outcomes included intensive care unit and hospital length of stay, and the Extended Glasgow Outcome Scale at hospital discharge. Results: Propofol and midazolam were the most commonly used sedatives. Propofol was more common than midazolam as first line therapy (35.4% v 25.6% respectively). Patients treated with propofol had similar Acute Physiology and Chronic Health Evaluation (APACHE) II and International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) scores to patients treated with midazolam, but lower Injury Severity Score (ISS) (median, 26 [IQR, 22-38] v 34 [IQR, 26-44]; P = 0.001). The use of propofol was more common in heavier patients, and midazolam use was strongly associated with opioid co-administration (OR, 12.9; 95% CI, 3.47-47.95; P < 0.001). Sixty-day mortality and hospital mortality were predicted by a higher IMPACT score (P < 0.001) and a higher ISS (P < 0.001), but, after adjustment, were not related to the choice of sedative agent. Conclusions: Propofol was used more often than midazolam, and large doses were common for both sedatives. The first choice was highly variable, was affected by injury severity, and was not independently associated with 60-day mortality.