Background: Postoperative pain management is a major concern and a significant component of postoperative care pathways for surgery patients. Methods: We performed a retrospective medical record review of 233 consecutive patients undergoing major colorectal surgery from October 2011 to January 2013 at an academic medical center. All patients were managed with similar enhanced recovery pathways; 66 patients received multimodal postsurgical pain management that included liposomal bupivacaine intraoperatively, and 167 patients received conventional pain management with intravenous opioids. Comparisons were made using t test and chi-square analysis with StatView (SAS Institute Inc.). Results: Patients receiving multimodal pain management with liposomal bupivacaine injected in the surgical site at the end of major colorectal procedures had lower postoperative pain scores and used significantly less opioids at 12, 24, 36, 48, 60, and 72 hours (P=0.03). Patients in the multimodal group also had a significantly decreased risk of opioid-related adverse events, with decreased use of antipruritic medications and antiemetic medications postoperatively. A significant decrease in length of postoperative hospital stay was seen in the multimodal group (7.2 vs 9.0 days, P=0.04). Conclusion: The use of multimodal pain management including liposomal bupivacaine during major colorectal surgeries improved postoperative outcomes, decreased lengths of stay, and increased bed availability. [ABSTRACT FROM AUTHOR]