Objective: We perform this protocol for randomized controlled trial to compare the efficacy of intrathecal morphine and local infiltration anesthesia (LIA) in the treatment of the postoperative pain after total knee replacement (TKR). Methods: This is a randomized controlled, single center trial which was performed from March 2019 to March 2020. This trial is conducted according to the SPIRIT Checklist of randomized researches. It is authorized via the Ethics Committee of Beijing Friendship Hospital (2019-P2-050-01). Eighty participants who undergo TKR were randomized into 2 groups. Intrathecal morphine group: 0.1 mg of the morphine was intrathecally injected, and the spinal anesthetic was injected at the same time in the group LIA; In the LIA group: the knee joint was infiltrated with epinephrine, ketorologic acid and ropivacaine in the process of operation, and the identical mixture was injected 2 bolus through the intraarticular catheter after operation. The main outcome variables were the visual analog scale and the consumption amount of opioid every 6-hour interval within 2 days postoperatively. The secondary outcome variables were the side effects associated with opioid, the length of hospital stay, motion range, and the loss of blood collected by the closed suction drainage. All the required analyses were carried out via applying the SPSS for Windows Version 19.0. Results: The clinical outcome variables between groups were shown inTable 1. Conclusion: This protocol will provide the evidence on which technique can achieve better analgesia after TKR.