Background: Pre-injury use of anticoagulant and antiplatelet medications is a significant risk factor for worse outcomes in patients with traumatic brain injury (TBI). These medications are commonly prescribed for conditions such as atrial fibrillation and venous thromboembolism. However, the prevalence and patterns of their use among TBI patients presenting to different levels of trauma centers remain inadequately characterized. Understanding these variations is crucial for risk stratification, protocol development, and resource allocation. Objective: This study aimed to determine the prevalence of pre-injury anticoagulant (AC) and antiplatelet (AP) medication use in adult TBI patients and to analyze how this prevalence varies across Level I, Level II, and Level III/IV trauma centers. Methods: A retrospective, multi-center cohort study was conducted using data from a statewide trauma registry over a three-year period. All adult patients (≥18 years) with a diagnosis of TBI (Abbreviated Injury Scale head region score ≥2) were included. Patients were categorized based on the level of the treating trauma center (Level I, II, or III/IV). The primary outcome was the documented use of any pre-injury AC (warfarin, direct oral anticoagulants - DOACs, heparinoids) or AP (aspirin, P2Y12 inhibitors) medication. Secondary analyses examined the specific types of medications, patient demographics, injury severity, and clinical outcomes (in-hospital mortality, neurosurgical intervention) across center levels. Results: Among 12,547 TBI patients analyzed, 2,831 (22.6%) were on pre-injury AC/AP therapy. Prevalence varied significantly by trauma center level: Level I centers had the highest prevalence at 25.8% (1,250/4,850), followed by Level II at 20.1% (1,020/5,075), and Level III/IV at 21.4% (561/2,622) (p < 0.001). Level I centers treated a significantly higher proportion of patients on DOACs (9.2% vs. 6.5% in Level II and 5.8% in Level III/IV, p<0.001) and had a higher mean patient age. While unadjusted mortality was higher in Level I centers (12.5% vs. 10.8% in Level II and 9.1% in Level III/IV), after adjusting for age, injury severity, and anticoagulant use, the risk-adjusted mortality odds were comparable. Patients on AC/AP therapy across all levels had higher mortality and rates of neurosurgical intervention compared to those not on such medications. Conclusion: The prevalence of pre-injury anticoagulant and antiplatelet use among TBI patients is substantial and varies systematically across trauma center levels. Level I centers manage a significantly higher burden of patients on these medications, particularly newer DOACs, reflecting patient complexity and referral patterns. These findings underscore the need for all trauma centers, regardless of level, to have protocols for rapid reversal of anticoagulation in TBI, while highlighting that Level I centers require enhanced readiness and resources to manage this high-risk population.