INTRODUCTION/PURPOSE: The purpose of this systematic review was to evaluate the effect of iron supplementation during total knee arthroplasty (TKA): (1) Is the iron supplementation necessary during TKA? (2) When is the optimal timing of iron supplementation? (3) Which is better, between orally and intravenously administered iron supplementation? And (4) What is the optimal dose of iron supplementation? MATERIALS AND METHODS: A rigorous and systematic approach was used and each of the selected studies was evaluated for methodological quality. Data about study design, total number of cases enrolled, iron administration method, timing, and dose were extracted. Change in hemoglobin and transfusion rates were extracted to evaluate the effectiveness of iron supplementation. RESULTS: Eleven studies were included in the final analysis. Most of studies reported that hemoglobin change between iron and control group did not show any difference. Only one study reported that iron supplementation could reduce the decrease in hemoglobin. However, transfusion rate showed a decrease in the iron supplementation group compared with the control group. There was no clear consensus on the optimum timing and dose of iron supplementation and intravenously administered iron was more effective than orally administered iron, especially in anemic patients. CONCLUSION: Iron supplementation is not clear as a way to raise hemoglobin levels after TKA, but an effective treatment for lowering transfusion rate, especially in patients with anemia. We could not determine the optimal timing and dose of the iron. Intravenously administered iron was similar to, or better than, orally administered iron for improving hemoglobin levels and transfusion rate.