Many factors are driving total knee arthroplasty to be performed more commonly as an outpatient (<24 hour discharge) procedure. Nonetheless, the safety of total knee replacements performed in the outpatient setting is not well established when compared with inpatient setting. The purpose of this study is to compare the postoperative outcomes of outpatient and inpatient total knee arthroplasties. The 2015 and 2016 American College of Surgeons National Surgical Quality Improvement Program data sets were queried to extract patients who underwent primary, elective, unilateral total knee arthroplasty. The primary outcome was serious adverse events defined by a composite outcome including: return to operating room, wound-related infection, thromboembolic event, renal failure, myocardial infarction, cardiac arrest requiring cardiopulmonary resuscitation, cerebrovascular accident, use of ventilator >48 hours, unplanned intubation, sepsis/septic shock, and death. Propensity matched analysis was used to adjust for potential confounding covariates. 1099 patients undergoing outpatient total knee arthroplasty (1% of total cases) were successfully matched to 1099 patients undergoing inpatient surgeries. The composite rate of serious adverse events was greater in outpatient procedures compared with inpatient procedures (3.18% vs 1.36%, p=0.005). In contrast, failure to rescue and readmission rates were not different between groups. Outpatient total knee arthroplasty is associated with a higher composite risk of serious adverse events than inpatient procedures. Anesthesiologists and surgeons should inform patients and discuss this information when obtaining consent for surgery and planning for discharge timing.