Objective.—To perform an observational study of the demographics, clinical factors, and therapeutic efficacy in patients presenting to the emergency department with a chief complaint of headache. Background.—Acute headache presentations to the emergency department are a therapeutic dilemma for physicians. Methods.—Patients presenting with nontraumatic headache to the emergency department of Hermann Hospital in Houston, Texas, during a 16-month period were prospectively ascertained by active and passive surveillance. The medical record was abstracted. Demographic and clinical information are presented with descriptive statistics. Relative benefit of individual therapies are compared with odds ratios (95% confidence intervals). Results.—Of the 38 730 patients who were prospectively screened, 455 presented with a chief complaint of headache. Seventy-six percent were women, and the mean age was 37 years. Non-Hispanic whites were more likely diagnosed with migraine compared with Hispanics or African Americans (P<.001). Three percent had subarachnoid hemorrhage. Neurologist follow-up was ordered in 10%. The median time in the emergency department was 265 minutes. With the initial treatment, 44% resolved, 47% improved, and 9% had no change; none worsened. In comparison with all other therapies used, there was a trend suggesting the superiority of antiemetics (odds ratio, 2.66; 95% confidence interval, 0.81 to 8.61). Acetaminophen was less helpful (odds ratio, 0.27; 95% confidence interval, 0.10 to 0.70). When comparing specific agents to therapies which could be used at home, antiemetics led to headache resolution most often (odds ratio, 3.18; 95% confidence interval, 1.40 to 7.22); ketorolac showed a similar trend (odds ratio, 2.05; 95% confidence interval, 0.86 to 4.89). Conclusions.—Headache in the emergency department is a phenomena of young women who spend a long time waiting and receive many tests. A variety of therapies are used. Antiemetics may be especially useful for headache resolution.