OBJECTIVE: To determine the response rate to triptans in alleviating "sinus headache" in patients with endoscopy- and computed tomography (CT)-negative sinus examinations. STUDY DESIGN: Prospective clinical trial. METHODS: Patients who presented to a tertiary care center Otolaryngology Department with primary complaints of facial pain, pressure, or headache localized over the area of the sinuses, and a self- or physician-diagnosis of "sinus headache" were enrolled. Patients underwent directed history, physical examination, rigid nasal endoscopy, a sinus CT scan, and completed a headache questionnaire. Those patients that had negative findings were treated empirically with triptans. Patients completed a headache diary for each headache, using a visual analogue scale to rate the headache before and after triptan use. Response was considered as significant improvement (greater than 50% reduction of pain), partial (25-50% reduction), and no response. RESULTS: Fifty-four patients were enrolled. Thirty-eight (69%) completed follow-up, 63% were women. The mean age was 41 years (23-70). Thirty-one patients (82%) had significant reduction of headache pain with triptan use. Thirty-five patients (92%) had a significant reduction in headache pain in response to migraine-directed therapy. Seventeen patients (31%) withdrew or failed to follow-up, often reluctant to accept a diagnosis of migraine. CONCLUSIONS: This study demonstrated that the demographics of patients with self-described "sinus headaches" who did not have findings of sinusitis on endoscopy and CT scan closely reflected the demographics of patients afflicted with migraines. It also showed that 82% of these patients had a significant response to empiric treatment for sinus headaches with triptans. These findings support that "sinus headaches" may represent migraines, and response to triptans may aid in diagnosis.