BACKGROUND: Rehabilitation is important for patients with moderate-to-severe traumatic brain injury (TBI). However, the timing of early rehabilitation initiation is ambiguous, and its safety and effectiveness are unknown. OBJECTIVE: To examine the effectiveness and safety of early rehabilitation in patients with moderate-to-severe TBI using propensity score analysis and a large database. DESIGN: Retrospective cohort study. SETTING: A large medical database (JMDC database) of tertiary care facilities was used to compare outcomes of early and delayed rehabilitation. PATIENTS: Patients aged between 20 and 90 years who were diagnosed with TBI were admitted to acute care hospitals. Inclusion criteria were patients undergoing rehabilitation within 7 days of admission with a Glasgow Coma Scale score of 3 to 12 on admission. This study included 3074 patients with moderate-to-severe TBI. INTERVENTIONS: Patients were classified into an early rehabilitation group (within 2 days of admission) or a delayed rehabilitation group (3 to 7 days postadmission), depending on when rehabilitation started after TBI. Rehabilitation was defined as any type or intensity of intervention provided by a physical, occupational, and/or speech/language therapist. Interventions were not controlled. MAIN OUTCOME MEASURE(S): The primary outcome was Barthel Index (BI) efficiency (BI gain/length of stay). Secondary outcomes included BI gain (discharge BI - admission BI), incidence of aspiration pneumonia complications during hospitalization, discharge to home, mortality, and length of stay. RESULTS: After applying inverse probability weighting with propensity scores, the total was 6152 patients. 3074 (50.0%) patients received early rehabilitation. The early rehabilitation group showed no difference in inpatient mortality (p = .438), improved BI efficiency (β = 0.86, p <
.002), and shorter length of stay (β = -5.00, p = .018). CONCLUSIONS: Early rehabilitation in patients with moderate-to-severe TBI is associated with more efficient functional improvement and reduced hospital stays without an increase in inpatient mortality.