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As concerns regarding health-care expenditure in the U.S. remain at the national forefront, outpatient arthroplasty is an appealing option for carefully selected patient populations. The purpose of this study was to determine the nationwide trends and complication rates associated with outpatient total knee arthroplasty (TKA) in comparison with standard inpatient TKA.We performed a retrospective review of the Humana subset of the PearlDiver Patient Record Database to identify patients who had undergone TKA (Current Procedural Terminology [CPT] code 27447) as either outpatients or inpatients from 2007 to 2015. The incidence of perioperative medical and surgical complications was determined by querying for relevant International Classification of Diseases, Ninth Revision (ICD-9) and CPT codes. Multivariate logistic regression analysis adjusted for age, sex, and Charlson Comorbidity Index (CCI) was used to calculate odds ratios (ORs) of complications among outpatients relative to inpatients treated with TKA.Cohorts of 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA were identified. The median age was in the 70 to 74-year age group in both cohorts. The incidence of outpatient TKA increased across the study period (R2 = 0.60, p = 0.015). After adjustment for age, sex, and CCI, outpatient TKAs were found to more likely be followed by tibial and/or femoral component revision due to a noninfectious cause (OR = 1.22, 95% confidence interval [CI] = 1.01 to 1.47; p = 0.039), explantation of the prosthesis (OR = 1.35, CI = 1.07 to 1.72; p = 0.013), irrigation and debridement (OR = 1.50, CI = 1.28 to 1.77; p < 0.001), and stiffness requiring manipulation under anesthesia (OR = 1.28, CI = 1.17 to 1.40; p < 0.001) within 1 year. Outpatient TKA was also more frequently associated with postoperative deep vein thrombosis (OR = 1.42, CI = 1.25 to 1.63; p < 0.001) and acute renal failure (OR = 1.13, CI = 1.01 to 1.25; p = 0.026).With the potential to minimize arthroplasty costs among healthy patients, outpatient TKA is an increasingly popular option. Nationwide data from a private insurance database demonstrated a higher risk of perioperative surgical and medical complications including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.