Standard multimodal pain management for anterior cruciate ligament reconstruction typically includes a combination of local anesthetics, nonsteroidal anti-inflammatory drugs, and opioids. Opioids present a substantial risk, and there is a rising number of prescription opioid-related overdoses in the United States. The goal of this study was to evaluate the quantity of opioids prescribed to patients who received liposomal bupivacaine as a component of their multi-modal pain regimen. The electronic medical records of patients who underwent anterior cruciate ligament reconstruction by a single surgeon at an urban hospital during a 2-year period were evaluated. Patients in the case group received liposomal bupivacaine and those in the control group did not. Statistical analysis of the number of pills prescribed and numeric pain rating scale scores was performed with a 2-tailed unequal variance t test. Statistical analysis of opioid prescription refills was performed with a chi-square test. A total of 67 patients were included. The mean number of 5-mg oxycodone tablets prescribed to the case group (9.29±10.29 tablets) was significantly lower (P<.01) compared with the number prescribed to the control group (66.26±37.13 tablets). Patients in the case group also were less likely to require an opioid prescription refill at the first follow-up appointment (P<.01; absolute risk reduction, 50%; number needed to treat, 2). Mean numeric pain rating scale score at 2 weeks was 2.8±2.1 in the case group and 3.8±2.4 in the control group (P=.09). Patients who received liposomal bupivacaine as part of multimodal pain management had significantly fewer opioid prescriptions. Despite the reduction in opioids prescribed, patients in the case group only showed a trend toward a reduction in pain at 2-week follow-up. [Orthopedics. 2021;44(2):e229-e235.].