Objective: This study aimed to investigate the relationship between abnormal intracranial findings on brain computed tomography and antiplatelet or anticoagulant use in patients with nontraumatic headache in the emergency department (ED). Methods: This was a single-center prospective observational study of patients admitted to the tertiary ED with complaints of nontraumatic headache between May 1, 2016 and September 1, 2016. Anticoagulant or antiplatelet drug use by the patient was recorded. Brain computed tomography (CT) results were categorized into two groups, abnormal results (CT positive) and no pathologic results (CT negative), and compared. The CT positive group included any pathological signs in the brain and the negative group was considered a normal read. A logistic regression analysis was used for evaluating the association of antiplatelets and anticoagulants with abnormal CT findings. Results: Of the 837 patients with nontraumatic headaches, 157 (18.8%) patients who underwent brain CT scanning were included. The mean age of the patients was 44.4±16.7 years. Eighty-eight (56.1%) of the patients were women. Of the 29 (18.4%) patients using antiplatelets or anticoagulants, 16 (55.2%) were in the CT positive group. There was a statistically significant difference between both groups in terms of drug use compared to the CT negative group (P<0.001). Factors affecting CT results were examined in logistic regression analysis and a statistically significant difference was found in the detection of positive results in antiplatelet or anticoagulant drug users (adjusted odds ratio, 2.478; 95% confidence interval, 1.006–6.102; P=0.048). Conclusion The use of antiplatelets or anticoagulants in patients admitted to the ED with nontraumatic headache is associated with an increased risk of abnormal intracranial results in brain CT.