Total Knee Replacement (TKR) surgery is one of the invasive procedures for patients with late-stage knee joint disorders. In the present study, economic efficiency was compared between uses of the 2nd and 3rd generation cephalosporins for the prophylaxis before and after the surgery using frequency analysis in terms of various factors such as medication costs, the number of days of antibiotic use and hospitalization due to TKR surgery. The results showed that the 3rd generation cephalosporins did not reduce the infection rate and total medication costs, but rather raised antibiotic cost in comparison with the 2nd ones. A frequent use of the 3rd ones is closely related to emergence of resistant bacterial strains. Therefore, we suggest that unnecessary prescriptions for the broad spectrum antibiotics should be avoided.