Introduction: When a stroke hospitalization follows soon after an Emergency Department (ED) treat-and-release visit for non-specific neurological complaints, a diagnostic error may have occurred. In this study, we sought to evaluate potential stroke misdiagnoses after ED treat-and-release headache visits. Methods: We conducted a retrospective cohort study using state-wide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005-2018 and New York 2005-2016. Using standard ICD codes, we identified adult patients discharged home from the ED with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of back pain or renal colic (negative control cohorts). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic), defined using validated ICD codes. We used Cox proportional hazards modeling to assess the relationship between the index ED visit reason and stroke hospitalization adjusting for demographics and vascular risk factors. Results: We identified 1,458,904 patients with an ED treat-and-release headache visit; mean age was 41 (SD: 17) and 70% were female. A total of 2,636 (0.18%) headache patients were hospitalized for stroke within 30 days. Stroke risk was higher among headache patients compared to patients diagnosed with renal colic (HR: 2.7; 95% CI, 2.3-3.1) or back pain (HR: 3.8; 95% CI, 3.6-4.1; Figure). Among patients <40 years of age, stroke risk was even higher among headache as compared to back pain (HR: 10; 95% CI, 7.7-13.1); no strokes occurred in renal colic patients <40 years of age. Conclusion: Approximately 1 in 500 patients discharged home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was 3-4 times higher after an ED visit for headache compared to back pain or renal colic. There may be opportunities to reduce diagnostic error among patients with ED visits for headache, particularly for those <40 years of age.