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Background: Platelet dysfunction has been attributed to progression of initial intracranial hemorrhage (ICH) on repeat head computed tomographic (RHCT) scans in patients on prehospital antiplatelet therapy. However, there is little emphasis on the effect of platelet count and progression of ICH in patients with traumatic brain injury. The aim of this study was to determine the platelet count cutoff for progression on RHCT and neurosurgical intervention in patients on antiplatelet therapy., Methods: We performed a prospective cohort analysis of all traumatic brain injury patients with an ICH on prehospital antiplatelet therapy. Antiplatelet therapy was defined as aspirin, clopidogrel, or a combination of both. Admission platelet count was recorded and used for analysis. Receiver operating characteristic curves were plotted to identify the optimal platelet count for progression on RHCT scan and neurosurgical intervention in patients on antiplatelet therapy., Results: A total of 264 patients were enrolled. Platelet count of 135,000/µL or less (area under the curve, 0.80) and platelet count of 95,000/µL or less (area under the curve, 0.92) were the optimal threshold points for progression on RHCT scan and neurosurgical intervention, respectively. Patients with platelet count of 135,000/µL or less were 12.4 times (95% confidence interval, 7.1-18.4) more likely to have progression on RHCT scan and patients with platelet count 95,000/µL or less were 31.5 times (95% confidence interval, 19.7-96.2) more likely to require neurosurgical intervention., Conclusion: A platelet count of less than 135,000/µL in patients on antiplatelet therapy is predictive of both radiographic and clinical worsening. This is a clinically relevant target intended to help tailor and improve management in patients on antiplatelet therapy., Level of Evidence: Therapeutic study, level III.