Abstract Patients with moderate to severe head injury and abnormal coagulation studies have a significantly higher risk of brain injury. The objective of this study was to determine the association of clinical suspicion of coagulopathy and intracranial injury (ICI) among patients sustaining blunt head trauma, including minor injuries. As part of the NEXUS II blunt head injury study, enrolled patients were prospectively evaluated for ICI and suspicion of coagulopathy. We examined the relationship between suspicion of coagulopathy and the presence of any clinically significant or “therapeutically inconsequential” ICI based on head computed tomography (CT) scan results. The NEXUS II study enrolled 13,728 patients, including 493 with suspicion of coagulopathy. Significant ICI was present in 46 (9.3%; 95% confidence interval [CI] 6.9–12.2) patients with suspected coagulopathy, and in 460 of 9863 (4.7%; 95% CI 4.3–5.1) patients without such suspicion. “Therapeutically inconsequential” findings were found on head CT scan in 74 patients, and 7 of these had suspected coagulopathy. Interventions including intubation, intracranial pressure monitoring, or craniotomy were performed in 5 of these 7 (71%; 95% CI 29–96) individuals, compared with only 3 of 67 (4%; 95% CI 1–12) patients without suspicion of coagulopathy. Initial clinical suspicion of coagulopathy, independent of laboratory confirmation, is associated with a greater prevalence of significant ICI injury after blunt head trauma; it also substantially increases the risk of morbidity despite the presence of an apparent “therapeutically inconsequential” injury. CT scanning of the head should be performed initially based on clinical suspicion of coagulopathy.