Thirty-six patients undergoing minimally-invasive total knee arthroplasty (TKA) desiring rapid recovery were randomized to follow either a multimodal analgesic protocol or patient-controlled analgesia (PCA) regimen, to compare the efficacy and safety of the two approaches. Results indicated that the use of a multimodal analgesic regimen led to significantly improved postoperative pain relief and patient satisfaction, decreased narcotic consumption and narcotic-related adverse events, and decreased time to achieve physical therapy milestones within the first 3 postoperative days, compared to patient-controlled analgesia (PCA) parenteral narcotics. These significant differences persisted at the 3-week postoperative assessment, but not at 6 weeks post-TKA.