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. To examine the effectiveness and safety of early rehabilitation in patients with moderate-to-severe TBI using propensity score analysis and a large database. Retrospective cohort study. A large medical database (JMDC database) of tertiary care facilities was used to compare outcomes of early and delayed rehabilitation. 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. 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. 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. 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 < .001), and shorter length of stay (β = -5.00, p = .018). 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.