Here we investigated the differences in clinical characteristics between head injury patients with and without preinjury antithrombotic therapy to clarify its effect to the clinical course and outcome. A total of 779 patients from January 2015 to December 2018 were included in this study. There were 60 patients with preinjury antithrombotic therapy. Patients’ characteristics, symptoms, and clinical findings on hospital arrival, surgically treated or not, and modified Rankin Scale at discharge were compared. Patients’ age and rate of fall related injury were significantly higher in patients with preinjury antithrombotic therapy. They also had significantly more patients who talked and deteriorated (T&D), higher rate of surgical treatment, and worse clinical outcome, although Glasgow Coma Scale on hospital arrival showed no difference. Preinjury antithrombotic therapy significantly increase the rate of T&D and surgical treatment. These findings highlight the effect of preinjury antithrombotic therapy on treating head injury and the importance of close observation and neutralization of antithrombotic drugs.