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Objective: Most of the fractures and dislocations are reduced in the emergency setting. Many drugs are available for procedural sedation and analgesia in the emergency department (ED); however, the adverse effects are still a common problem. The aim of our study was to compare the 2 drug combinations., Method: We performed a prospective, randomized, double-blinded, placebo-controlled trial of patients presenting to the ED after a traumatic event and required urgent reduction either for a fracture or dislocation. Patients were randomized to midazolam-fentanyl (MF) group or ketamine-low-dose midazolam (KM) group. Hypoxia, duration of hypoxia, need for oxygen, time to onset of sedation, recovery time, pain scores during reduction, and sedation depth were set as primary outcome measures and were recorded., Results: A total of 498 patients who presented to ED with extremity injury and required closed reduction were assessed; 130 of them were approached for eligibility and 69 patients were excluded. The remaining 61 patients were randomized to either KM group (n = 31) or MF group (n = 30). Hypoxia and duration of hypoxia were significantly lower in the KM group compared with the MF group. Patients in the KM group reported significantly lower pain scores during reduction; however, adverse effects were higher compared with MF group., Conclusion: Both drug combinations can be effectively used for procedural sedation and analgesia; however, with lower risk for hypoxia and lower pain scores, KM combination stands as a reasonable choice for orthopedic interventions in the emergency unit., (Copyright © 2013 Elsevier Inc. All rights reserved.)