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To establish the safety and efficacy of single-dose intraoperative intravenous (IV) acetaminophen in postoperative pain management following adenotonsillectomy in addition to a standardized regimen of oral pain medication.Randomized, controlled prospective clinical trial.Single academic medical center.Patients between the ages of 3 and 17 years scheduled for tonsillectomy or adenotonsillectomy by a single surgeon between December 2014 and November 2016 were recruited. Patients were randomly assigned to 1 of 2 groups; group 1 received a single intraoperative dose of IV acetaminophen, and group 2 did not. Induction and maintenance of anesthesia, as well as operative technique, were standardized. Nursing pain scores, pain medications administered, and recovery times were reviewed during the 24-hour postoperative period. Postoperative pain regimen included standing alternating oral acetaminophen and ibuprofen.In total, 260 patients were included in the study, and 131 (50.4%) received a single intraoperative dose of IV acetaminophen. Patients receiving IV acetaminophen were more likely to experience postoperative nausea and vomiting than patients who did not receive IV acetaminophen (1.53% vs 0.00%, P = .016). There were no significant differences noted for postoperative pain scores, requirements for breakthrough pain medications, time to discharge from the recovery room or hospital, or postoperative complications.The use of a single intraoperative dose of IV acetaminophen was associated with minimal additional adverse effects. However, a single intraoperative IV dose of acetaminophen added to standard narcotic and nonnarcotic pain medication does not provide a statistically significant improvement in pain control.