211 patients scheduled for total knee arthroplasty were randomized to one of three multimodal analgesia regimens: oral acetaminophen and periarticular infiltration with a standard knee injection cocktail, oral acetaminophen and periarticular infiltration with liposomal bupivacaine, and intravenous acetaminophen and periarticular infiltration with a standard knee injection cocktail. Primary outcomes included pain scores, narcotic consumption, and opioid-related adverse events. Results demonstrated no significant differences in pain scores and opioid-related side-effects between the three groups, while total narcotic consumption within the first 24 hours was significantly greater in the group administered liposomal bupivacaine compared to the other two groups.