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Background: The overall satisfaction of patients after total knee arthroplasty (TKA) is approximately 80%, and current studies have demonstrated that patients with depression may have lower patient satisfaction. The purpose of this study was to determine whether perioperative psychological intervention in patients with depression improves the clinical outcomes and patient satisfaction in patients undergoing TKA.Methods: Six hundred patients who underwent primary TKA from May 2016 to January 2018 were prospectively screened for eligibility. A preoperative psychological evaluation was conducted by a psychiatrist to evaluate each patient's psychological status. Patients who were diagnosed with depression were randomly divided into 2 groups: the intervention group (patients received psychological interventions that were administered by a psychiatrist at the first visit before surgery and from then on) and the control group (patients received routine TKA care without psychological interventions). The primary outcome was patient satisfaction at 6 months postoperatively. The secondary outcomes were patient satisfaction at 2 years postoperatively as well as the Hospital for Special Surgery (HSS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and range of motion at 6 months and 2 years postoperatively.Results: Fifty-three patients with depression were identified. Fifty-one patients were enrolled in the randomized controlled trial. Two patients were lost to follow-up at 6 months after surgery. Therefore, 49 patients (25 in the intervention group and 24 in the control group) remained in the final analysis. At 6 months postoperatively, statistical differences in patient satisfaction were identified between the 2 groups (88.0% in the intervention group compared with 62.5% in the control group; odds ratio = 4.40; 95% confidence interval, 1.02 to 18.99). There was a significant improvement in the Self-Rating Depression Scale (SDS) score (the reduction rate was 51.97% in the intervention group compared with 17.35% in the control group) and the Symptom Checklist 90 Revised (SCL-90-R) subscore for depression (the reduction rate was 44.66% in the intervention group compared with 15.73% in the control group). The clinical outcomes, including the WOMAC scores, the HSS scores, and maximal range of motion, in the intervention group had improved significantly more compared with those in the control group.Conclusions: Psychological interventions during the perioperative period can improve patient satisfaction in patients with depression who undergo TKA. Therefore, psychological intervention and management may be beneficial for patients with depression who are planning to undergo TKA.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]