84 patients scheduled for anterior cruciate ligament (ACL) reconstruction were randomized to multimodal postoperative analgesia including infiltration analgesia with liposomal bupivacaine or a femoral nerve block. The purpose of this study was to determine if liposomal bupivacaine infiltration offered noninferior analgesic efficacy compared to a femoral nerve block, assessed over the first 4 days postoperatively. In the period of 5-8 hours after surgery, pain scores were significantly higher among those treated with liposomal bupivacaine infiltration compared to those who received a femoral nerve block; otherwise, pain scores and analgesic consumption did not significantly differ between groups.