270 patients scheduled for total knee arthroplasty were randomized to a control group or one of six drug combination groups. The purpose of this study was to assess the analgesic and clinical effects of various periarticular drug combinations in order to determine optimal drug combinations. Pain, opioid consumption, C-reactive protein level, range of motion, and incidence of complications were measured. Results indicated that patients who had received ropivacaine, morphine, and ketorolac, with or without methylprednisolone, in addition to epinephrine, cefazolin, and saline experienced significantly greater pain relief over the first 12 postoperative hours. The addition of methylprednisolone was also associated with significantly greater range of motion, as well as significantly lower levels of C-reactive proteins, though did not significantly impact pain relief as compared to injections without methylprednisolone.