Background Liposomal bupivacaine (LB) is increasingly being used for postoperative pain control, but there are conflicting efficacy data when compared with immediate-release bupivacaine (IRB). Objective To evaluate the comparative efficacies of LB and IRB for postoperative pain control in order to assess the formulary status of LB at our institution. Methods A single-center, retrospective, institutional review board–approved, noninferiority matched cohort study at a tertiary care academic medical center. Adult surgical patients admitted for >24 hours who received LB or IRB were included. The primary outcome was total opioid consumption within 24 hours postoperatively. Secondary outcomes included total opioid consumption within 72 hours postoperatively, nonopioid analgesic use within 24 and 72 hours postoperatively, time to rescue analgesic use, and postoperative length of stay (LOS). Results A total of 326 patients were included in the matched cohort. Median 24-hour opioid consumption was significantly lower in the IRB group compared with the LB group (81 mg [30, 153] vs 103 mg [46, 241]; P = 0.01). Patients receiving IRB compared with LB also had a decrease in total opioid consumption 72 hours postoperatively (110 mg [45, 258] vs 165 mg [68, 402]; P = 0.005) and shorter postoperative LOS (2.8 days [1.7, 4] vs 3.3 days [2, 5.1]; P < 0.001). There was no difference in time to rescue analgesic use. Conclusion and Relevance Across a variety of surgical procedures, administration of IRB compared with LB was associated with a reduction in total opioid consumption within 24 and 72 hours postoperatively and shorter LOS in adult surgical patients.