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Objective: To investigate the impact of the number of drugs on rehabilitation outcomes for patients with acute traumatic brain injury., Design: Retrospective cohort study., Setting: Hospital-based database created by the Japan Medical Data Center., Participants: Patients with acute traumatic brain injury admitted between April 2014 and November 2017., Methods: Analysis of relationships among 1-5 and ≥ 6 drugs as well as clinical outcomes in 2603 patients., Main Outcome Measurements: The primary outcome was defined as the Barthel index efficiency, and the secondary outcome was Barthel index gain and length of hospital stay., Results: Median Barthel index score on admission was 40. Barthel index efficiency and Barthel index gain were significantly higher in the group that had taken 1-5 drugs than in the group that had taken ≥6 drugs on admission (median: 1.19 vs 0.50, 20.0 vs 10.0). Also, the group that had taken 1-5 drugs had a significantly shorter length of hospital stay than in the group that had taken ≥6 drugs on admission (median 11.0 vs 14.0). Moreover, multiple linear regression analysis showed that having taken ≥6 drugs on admission was independently associated with Barthel index efficiency, Barthel index gain, and length of stay., Conclusions: Taking≥6 drugs for acute traumatic brain injury was associated with lower Barthel index efficiency, lower Barthel index gain, and longer length of stay than taking 1-5 drugs., (© 2020 American Academy of Physical Medicine and Rehabilitation.)