Background: Controlling postoperative pain and improving outcomes after total hip arthroplasty (THA) remain an important challenge, which affects the functional recovery of the hip. Objectives: To assess the effect of preemptive administration of the selective cyclooxygenase-2 inhibitor parecoxib sodium (PS) after THA. Study Design: A prospective, randomized, double-blinded clinical trial. Setting: An academic medical center. Methods: This randomized double-blind clinical trial compared postoperative analgesia intervention for unilateral primary THA. Patients were assigned in a 1:1 ratio to the PS group and the control group. The PS group received 40 mg dose of PS 30 minutes before incision, 12 hours after THA, and every 12 hours for 2 days postoperatively, and the control group received normal saline solution at the same time point. In addition, both groups received patient-controlled intravenous analgesia of morphine. Perioperative visual analog scale (VAS) scores, cumulative morphine consumption, functional recovery, perioperative bleeding risk, and the selected indicators of the inflammatory response were compared between the PS group and the control group. Results: From October 2014 to June 2015, 180 patients undergoing unilateral primary THA were screened for this prospective clinical trial. A total of 141 patients were enrolled and randomly assigned into the PS group (n = 69) and the control group (n = 72). Compared with the control group, VAS scores at rest were significantly lower in the PS group at 4, 12, and 24 hours after surgery, and VAS scores during movement were also lower in the PS group at 4, 12, 24, 36, and 48 hours after surgery (all P< 0.001). Both the cumulative morphine consumption and its associated nausea and vomiting were reduced in the PS group (P< 0.001 and P= 0.021, respectively). The length of hospitalization in the PS group was shorter than the control group (PS group 5.91 +/- 1.15 days, control group 6.41 +/- 1.49 days; P= 0.019). The PS group had lower body temperature than the control group at postoperative day (POD) 1 (P= 0.003) and POD 3 (P= 0.001), and the levels of high-sensitivity C-reactive protein in the PS group at POD 3 (P= 0.016) and POD 6 (P= 0.006) were also lower than those in the control group. The concentration of interleukin (IL)-6 and IL-10 were significantly different between the 2 groups (IL-6, P= 0.007; IL-10, P= 0.006) on the first day postoperatively. The PS group was not significantly different from the control group with respect to any outcomes: blood loss, postoperative blood drainage and blood transfusion, and number of days needed to accomplish straight-leg raising and off-bed exercise. Limitations: PS was used only until POD 2, and there was no long-term follow-up. Conclusions: Perioperative administration of PS is an effective addition to a multimodal regimen that alleviates postoperative pain, reduces the cumulative morphine consumption, length of hospitalization, and perioperative inflammatory response, without increasing perioperative bleeding risk.