PurposeDespite the increase in outpatient total knee arthroplasty (TKA) procedures, many patients are still discharged to non‐home locations following index surgery. The ability to accurately predict non‐home discharge (NHD) following TKAs has the potential to promote a reduction in associated adverse events and excess healthcare costs. This study aimed to evaluate whether a machine learning (ML) model could outperform the American College of Surgeons (ACS) Risk Calculator in predicting NHD following TKA, using the same set of clinical variables. We hypothesised that the ML model would outperform the ACS Risk Calculator.MethodsData from 365,240 patients who underwent a primary TKA between 2013 and 2020 were extracted from the ACS‐National Surgical Quality Improvement Program database and used to develop an artificial neural network (ANN) to predict discharge disposition following primary TKA. The ANN and ACS calculator were assessed and compared using discrimination, calibration and decision curve analysis.ResultsAge (>68 years), BMI (>35.5 kg/m2) and ASA Class (≥2) were found to be the most important variables in predicting NHD following TKA. When compared to the ACS calculator, the ANN model demonstrated a significantly superior ability to distinguish the area under the receiver operating characteristic curve (AUC) among NHD patients and provided probability predictions well aligned with the true outcomes (AUCANN = 0.69, AUCACS = 0.50, p = 0.002, slopeANN = 0.85, slopeACS = 4.46, interceptANN = 0.04, and interceptACS = 0.06).ConclusionOur findings support the hypothesis that machine learning models outperform the ACS Risk Calculator in predicting non‐home discharge after TKA, even when constrained to the same clinical variables. Our findings underscore the potential benefits of integrating machine learning models into clinical practice for improving preoperative patient risk identification, optimisation, counselling and clinical decision‐making.Level of EvidenceIII