139 adult patients scheduled for primary, unilateral total knee arthroplasty (TKA) were randomized to receive a local infiltration analgesia (LIA) of aqueous bupivacaine (HCl) with or without liposomal bupivacaine (LB). The outcomes of interest included the proportion of opioid-free patients in the first 24 hours, total opioid consumption, area under curve (AUC) of pain intensity on a Visual Analog Scale, discharge readiness, satisfaction with pain treatment, ambulation, the timed up and go (TUG) test, and the incidence of adverse events. Results revealed significantly higher proportion of opioid-free patients, lower opioid consumption and pain intensity, higher discharge readiness and higher patient satisfaction in the LIA with LB group compared to the LIA without LB group. No significant differences in ambulation or the TUG test were observed between the two groups. The incidence of adverse events was similar in both groups.