Staged bilateral total knee arthroplasty (TKA) may provide an ideal clinical model for the study of central sensitization. In staged TKA, hyperalgesia may be induced as a result of repeated surgical injury possibly via central sensitization, which can decrease functional outcomes. Therefore, we hypothesized that in staged bilateral TKA, patients would have greater pain in the second operated knee than in the first. Thirty patients undergoing staged bilateral TKA at a 1-week interval were enrolled. Postoperative pain, which was reported on the basis of a visual analog scale (VAS; primary outcome) at rest and at maximum knee flexion, and the amount of patient-controlled analgesic (i.v. fentanyl) and rescue analgesic (i.v. ketoprofen; secondary outcomes) administered during the 48 h after the operation, were compared between the first and second TKA. VAS scores at rest and at maximum knee flexion were greater on the second operated knee (P<.001 and P<.01, respectively). The cumulative amounts of patient-controlled analgesic and the rescue analgesic were greater in the second than in the first TKA (P<.001 and P<.05, respectively). Patients undergoing staged bilateral TKA experience greater postoperative pain in the second operated knee than the first. This suggests extension of hyperalgesia beyond the initially injured site to remote regions after surgical injury, in which central sensitization may be involved. Therapeutic approaches to reduce such hyperalgesia induced in the course of staged operations are required.