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Introduction: Fentanyl is a lipid soluble, highly potent opioid. The lipid solubility of fentanyl makes it an ideal opioid to be administrated by inhalation. The current study compared ketamine infusion and nebulized fentanyl in bone fracture pain relief. Methods: In this double-blind, randomized clinical trial, patients aged 18 to 55 years who were admitted to the emergency department (ED) with limb fracture were recruited. A total of 127 patients were included in the study, 51.1% (65) of whom were male and 48.9% (62) of whom were female. The patients were divided equally into two groups: Group I received 100 cm3 IV infusion of normal saline and 4 μg/kg of 50 μg/ml nebulized fentanyl; Group II received 0.4 mg/kg ketamine in 10 min and 5 cm3 nebulized normal saline. Pain was assessed using a visual analog scale just before treatment and 5, 10, 15, 30, and 60 min post-treatment. Results: Before intervention, the pain scores of both groups showed no significant difference. However, log linear analysis in both groups showed a significantly decrement during the follow up (60 min) (p