Abstract Background Careful pre- and post-operative management can allow surgeons to perform outpatient TKA, making this a more affordable procedure. The aim of the present meta-analysis is to compare outpatient and inpatient TKA. Methods A systematic search of the literature was performed in July 2020 on PubMed, Web of Science, Cochrane library, and on the grey literature databases. The papers collected were used for a meta-analysis comparing outpatient and inpatient TKA in terms of complication and readmission rates. Risk of bias and quality of evidence were defined according to Cochrane guidelines. Results The literature search resulted in 4107 articles; of these, 8 articles were used for the meta-analysis. A total of 212,632 patients were included, 6607 of whom were TKA outpatients. The overall complication rate for outpatient TKAs was 16.1%, while inpatient TKAs had an overall lower complication rate of 10.5% (p = 0.003). The readmission rate was 4.9% in outpatient TKAs and 5.9% in inpatient TKAs. Only 3 studies reported the number of deaths, which accounted for 0%. The included studies presented a moderate risk of bias, and according to GRADE guidelines, the level of evidence for complications and readmissions was very low. Conclusions This meta-analysis documented that outpatient TKA led to an increased number of complications although there were no differences in the number of readmissions. However, future high-level studies are needed to confirm results and indications for the outpatient approach, since the studies currently available have a moderate risk of bias and a very low quality of evidence.