Purpose: Preoperative acetaminophen is recognized as an effective part of the multimodal approach to perioperative pain management. The present study, conducted between April 12, 2018 and February 14, 2019, examined whether there are differences in patient-reported pain, postoperative opioid consumption, negative opioid effects, length of postanesthesia care unit stay, and patient satisfaction with pain control between patients who receive intravenous (IV) acetaminophen and patients who receive oral acetaminophen. Design: This double-blinded, randomized controlled trial was conducted among 120 patients undergoing outpatient surgery. Methods: Patients were randomized to receive preoperatively either intravenous (IV) acetaminophen (and oral placebo) or oral acetaminophen (and IV placebo). Results were analyzed using SPSS statistical software; statistical analyses consisted of Mann-Whitney U test, independent samples t test, and c2 test. In all analyses, a P value less than .05 was considered significant. Findings: There were no significant differences in any outcome measures based on the route of acetaminophen administration. Conclusions: The findings of the present study support the practice of administering oral acetaminophen, as opposed to IV acetaminophen, preoperatively as part of the multimodal approach to manage postoperative pain in patients able to tolerate preoperative oral medications. (C)& nbsp;2020 American Society of PeriAnesthesia Nurses. Published by Elsevier, Inc. All rights reserved.