Background: Multimodal pain management within enhanced recovery after surgery (ERAS) protocols is designed to decrease opioid use, promote mobilization, and decrease postoperative complications. Objectives: To evaluate the role of intravenous (IV) versus oral (PO) acetaminophen within an established ERAS protocol in colorectal surgery. Study Design: This was a retrospective observational study. Setting: This research took place within an established perioperative colorectal surgery protocol. Methods: A total of 91 consecutive elective colorectal resections performed according to an ERAS protocol using only IV acetaminophen (IV group) were compared with 84 consecutive resections performed using one dose of IV acetaminophen followed by subsequent administration of oral acetaminophen (PO group). Our multimodal pain management strategy also included transverse abdominis plane blocks, celecoxib, and ketorolac medications for both groups. Opioid requirements, maximum and average daily pain scores by the Visual Analog Scale, and postoperative outcomes were compared between groups. Results: There were no differences in maximum or average pain scores on postoperative days 0-3 or at time of discharge between IV and PO groups. Compared with the IV acetaminophen only group, the PO group received significantly more perioperative opioids through 72 hours postoperatively (68.8 oral morphine equivalents [OME] IV group vs. 93.7 OME PO group; P < 0.0001), were more likely to require opioid patient-controlled analgesia (8.9% IV group vs. 46.4% PO group; P < 0.0001), and were more likely to experience postoperative nausea and vomiting (33.0% IV group vs. 48.8% PO group; P = 0.0449). Limitations: Significant limitations include the studies’ retrospective nature and that it was performed at a single institution. Conclusions: Restriction of IV acetaminophen within an ERAS protocol in colorectal surgery was associated with increased opioid use, greater need for opioid patient-controlled analgesia, and increased incidence of postoperative nausea and vomiting. IV acetaminophen may be superior to oral acetaminophen in the early postoperative setting. Key words: Perioperative pain management, enhanced recovery after surgery, acetaminophen, multimodal pain control, nonopioid