To determine whether lower extremity (LE) fracture fixation technique & timing (≤ 24 vs > 24 hours) impact neurologic outcomes in TBI patients. A prospective observational study was conducted across 30 trauma centers. Inclusion criteria were age ≥ 18, head abbreviated injury scale (AIS) score > 2, and a diaphyseal femur or tibia fracture requiring external fixation (Ex-Fix), intramedullary nailing (IMN) or open reduction and internal fixation (ORIF). The analysis was conducted using ANOVA, Kruskal-Wallis, and multivariable regression models. Neurologic outcomes were measured by discharge Ranchos Los Amigos Revised Score (RLAS-R). Of the 520 patients enrolled, 358 underwent Ex-Fix, IMN or ORIF as definitive management. Head AIS was similar among cohorts. The Ex-Fix group experienced more severe LE injuries (AIS 4-5) compared to the IMN group (16% vs 3%, p = 0.01) but not the ORIF group (16% vs. 6%, p = 0.1). Time to operative intervention varied between the cohorts with the longest time to intervention for the IMN group (median hours: Ex-Fix 15 [8-24] vs. ORIF 26 [12-85] vs. IMN 31[12-70], p < 0.001). The discharge RLAS-R score distribution was similar across the groups. After adjusting for confounders, neither method nor timing of LE fixation influenced the discharge RLAS-R. Instead, increasing age and head AIS score were associated with a lower discharge RLAS-R score (OR 1.02, 95% CI 1.002-1.03 and OR 2.37, 95% CI 1.75-3.22) and a higher GCS motor score on admission (OR 0.84, 95% CI 0.73,0.97) was associated with higher RLAS-R score at discharge. Neurologic outcomes in TBI are impacted by severity of the head injury and not the fracture fixation technique or timing. Therefore, the strategy of definitive fixation of LE fractures should be dictated by patient physiology and the anatomy of the injured extremity and not by the concern for worsening neurologic outcomes in TBI patients. Level III (Prognostic/Epidemiological).