60 patients undergoing total knee arthroplasty (TKA) were randomized to one of three groups to examine the effects of S(+)- ketamine on postoperative pain. Patients were randomized to receive intra-articular injections of 0.25 mg.kg of S(+)- ketamine diluted in 20 mL of saline solution 0.9% (group A), 0.5 mg.kg of S(+)- ketamine diluted in 20 mL of saline solution 0.9% (group B), or 20 mL of intra-articular saline 0.9% (group C) immediately after surgery. Over 24 hours, there was no difference between the three groups for intensity of pain, analgesia consumption and adverse events. Group A demonstrated a non-significant trend towards lower pain scores, less consumption of rescue analgesia, and longer time before additional analgesia was needed.