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To compare propofol with ketamine sedation delivered by pediatric intensivists during painful procedures in the pediatric critical care department (PCCD).Prospective 15-month study.An 18-bed multidisciplinary, university-affiliated PCCD.All children were randomized to the propofol or ketamine protocol according to prescheduled procedure dates. Propofol was delivered by continuous infusion after a loading bolus dose and a minidose of lidocaine (PL). Ketamine was given as a bolus injection together with midazolam and fentanyl (KMF). Repeated bolus doses of both drugs were given to achieve the desired level of anesthesia. The studied variables included procedures performed, anesthetic drug doses, procedure and recovery durations, and side effect occurrence. The patient’s parents, PCCD nurse and resident physician, pediatric intensivist, and the physician performing the procedure graded the adequacy of anesthesia.Of the 105 procedures in 98 children, PL sedation was used in 58 procedures, and KMF was used in 47. Recovery time was 23 mins for PL and 50 mins for KMF, and total PCCD monitoring was 43 mins for PL and 70 mins for KMF. Five children (10.6%) in the KMF group and in none in the PL group experienced discomfort during emergence from sedation. Transient decreases in blood pressure, partial airway obstruction, and apnea were more frequent in the PL than in the KMF sedation. All procedures were successfully completed, and no child recalled undergoing the procedure. The overall sedation adequacy score was 97% for PL and 92% for KMF (p < .05).Both PL and KMF anesthesia are effective in optimizing comfort in children undergoing painful procedures. PL scored better by all evaluators, recovery from PL anesthesia after procedural sedation was more rapid, total PCCD stay was shorter with PL, and emergence from PL was smoother than with KMF. Because transient respiratory depression and hypotension are associated with PL, it is considered safe only in a monitored environment (e.g., a PCCD).