Aims There is wide variation in opioid prescribing patterns after common surgical procedures. This study examines outcomes for beneficiaries undergoing hospital outpatient department (HOPD) procedures using liposomal bupivacaine (LB) for control of post-surgical pain. As a non-opioid surgical analgesic, LB may afford beneficial outcomes for reducing subsequent opioid use and improving post-surgical service use outcomes. Methods This retrospective cohort comparison study analyzed 100% Medicare claims data from 2014–2019. HOPD claims were matched to approximately 100 of the most common surgical procedures where LB was utilized. Within these procedures, a one-to-many, with replacement propensity score matching model was used to control for possible selection bias. By procedure, those claims which were identified as using LB for control of post-surgical pain were matched to those not receiving LB. Outcomes were the probability of a subsequent Part D opioid prescription fill, emergency department (ED) visit, and short-term acute care hospital admission. Results Higher provider use rates of LB are significantly correlated with a decrease in post-HOPD opioid use and a reduction in post-operative ED visits. For each 10% increase in LB use rate by a given provider, Part D opioid events by Day 30 decreased by 2.6 percentage points and by 2.1 percentage points by day 90 (p < .01). Similarly, for each 10% increase in provider LB use rate, there is a 0.4 percentage point reduction in post-operative ED use by day 30 (p < .01) and a 0.3 percentage point reduction by day 90 (p < .05). Limitations Part D data only indicate that a prescription was filled, not whether the drug was taken. Conclusions Increased provider use of LB is correlated with improved patient outcomes in real-world provider experience with the Medicare population for many outpatient procedures. Policies that support increased provider use of LB should reduce reliance on opioid drugs for post-surgical pain management.