Object: Ketamine is an agent used broadly for pediatric procedural sedation and analgesia(PSA) in emergency departments. As choosing between intravenous (IV) and intramuscular (IM) injections is a matter of concern, we did comparison between two methods in terms of their efficacy and the rate of complications. Design: Sedation by Ketamine was performed according to standard guidelines. A nurse blinded to the intervention was presented at the side of the patients during the whole procedure and not only recorded the routine nursing observations and evaluations, but also any abnormal conditions until the patient recovered to his/her pre-procedure state. Venipuncture was performed for all patients to ensure from blindness of the nurses and physicians. Setting: This single-blind clinical trial was conducted within three months to 15 years old children, weighted more than 5 kilograms, and required PSA for short and painful emergency procedures, who presented to the emergency departments of Imam Reza and Hasheminejad Hospitals, Mashhad, Iran. Before any intervention, administered medication and its complications were thoroughly explained for their parents and written informed consent was given from them. Participant: 240 children were recruited using convenience sampling. They were randomly allocated in two groups of 120 patients by using block randomization method. Subjects with a history of allergy to Ketamine, severe cardiovascular diseases, thyroid disorders, head injury, central nervous system (CNS) disorders, glaucoma or acute globe injuries, history or evidence of psychosis, obstructive sleep apnea, active pulmonary diseases such as upper respiratory tract infection, tracheal stenosis or surgery, needed procedures associated with stimulation of posterior pharyngeal region, and those who were not willing to participate were excluded from the study. Intervention: The first group of patients received IV Ketamine (1.5 mg/kg, Infusion by 100 milliliter normal saline; maximum dose 200 mg), and the second took as IM (4 mg/kg; maximum dose 200 mg). Main outcome measures: Indications for use, dose, side effects and efficacy of the medications as well as duration of the procedure and time to recovery were compared between two groups. At the end of the procedure, a specialist, who was blinded to the intervention, rated the efficacy of medicine in pain management and sedation as excellent (full sedation, immobility, and analgesia during the whole procedure), moderate (slight movements due to pain without interfering to procedure), and poor (movements associated with pain that interfered in the procedure).