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 multimodal 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 analy-sis 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.