We evaluate the patient demographics, perioperative outcomes, in-hospital complications, and assess recent national trends in clinically depressed and non-depressed patients undergoing primary total knee arthroplasty (TKA). Using the National Hospital Discharge Survey from 2001 and 2010, patients undergoing primary TKA in the United States were identified based upon the diagnosis of depression. Differences in gender, patient-demographics, comorbidities, complications, length of stay, and discharge disposition were analyzed. A total of 32,761 TKA patients were identified, consisting of 1,880 patients with a diagnosis of depression and 30,881 patients without. The depression group had an average age significantly younger than the non-depression cohort (p < 0.01). The depression group contained a significantly greater percentage of females when compared to the non-depression group. The non-depression group had a significantly greater percentage of African-Americans (p < 0.01), and a significantly smaller percentage of Caucasians (p < 0.01). Our findings contribute to the literature on the role of depression on perioperative outcomes of TKA. (Journal of Surgical Orthopaedic Advances 30(1):007-009, 2021).