Objective: To describe the clinical characteristics of a combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department (ED) patients. Methods: This was a prospective, observational trial, conducted in the ED of an urban level II trauma center. Patients ≥ 18 years of age requiring procedural sedation and analgesia were eligible, and enrolled patients received 0.07 mg/kg of intravenous midazolam followed by 2 mg/kg of intravenous ketamine. Vital signs were recorded at regular intervals. The adequacy of sedation, adverse effects, patient satisfaction, and time to reach discharge alertness were determined. Descriptive statistics were calculated using statistical analysis software. Results: Seventy-seven patients were enrolled. Three were excluded due to protocol violations, three due to lack of documentation, and one due to subcutaneous infiltration of ketamine, leaving 70 patients for analysis. The average age was 31 years, and 41 (59%) were female. Indications for procedural sedation and analgesia included abscess incision and drainage (66%), fracture/joint reduction (26%), and other (8%). The mean dose of midazolam was 5.6 ± 1.4 mg and the mean dose of ketamine was 159 ± 42 mg. The mean time to achieve discharge criteria was 64 ± 24 minutes. Fivepatients experienced mild emergence reactions, but there were no episodes of hallucinations, delirium, or other serious emergence reactions. Eighteen (25%) patients recalled dreaming while sedated; twelve (17%) were described as pleasant, two (3%) unpleasant, three (4%) both pleasant and unpleasant, and one (1%) neither pleasant nor unpleasant. There were four (6%) cases of respiratory compromise, two (3%) episodes of emesis, and one (1%) case of myoclonia. All of these were transient and did not result in a change in the patient's disposition. Only one (1%) patient indicated that she was not satisfied with the sedation regimen. Conclusions: The combination of midazolam and ketamine provides effective procedural sedation and analgesia in adult ED patients, and appears to be safe.