A prospective randomized clinical trial was performed in two centers to compare the effect of systemic cefuroxime and cefuroxime in bone cement in the prophylaxis of infection after total joint arthroplasty. In two comparable groups comprising 200 and 201 patients, there was no statistically significant difference in the incidence of superficial wound infection. The early deep infection rate was 1%, with no difference detected between the group that received antibiotic in bone cement and the group that received systemic antibiotic. There were no late deep infections. It is concluded that cefuroxime given systemically or in bone cement is an effective antibiotic in the prophylaxis of infection after total joint arthroplasty.