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The efficacy of cefuroxime was compared with the efficacy of cefazolin for prophylaxis against postoperative wound infection in a prospective, double-blind, multicenter study of 1354 patients who had had elective primary or revision total hip or knee arthroplasty. The patients were randomly assigned to receive either 1.5 grams of cefuroxime followed by 750 milligrams eight and sixteen hours later (for a total of one day of antibiotic treatment), or one gram of cefazolin every eight hours for nine doses (for a total of three days of antibiotic treatment). The first dose of each drug was administered fifteen to sixty minutes before the operative incision was made (for a primary operation) or after tissue samples had been obtained for culture (for a revision procedure). After the operation, the patients were assessed daily while hospitalized and then at two to three months and one year after the operation. Demographic characteristics and risk factors were similar in the two groups. For the patients who had had a primary hip arthroplasty, the rate of deep wound infection was 0.5 per cent (one of 187) for those who had received cefuroxime and 1.2 per cent (two of 168) for those who had received cefazolin. For the patients who had had a primary knee arthroplasty, the rate of deep wound infection was 0.6 per cent (one of 178) for those who had received cefuroxime and 1.4 per cent (three of 207) for those who had received cefazolin. No evidence of a superficial or deep wound infection was observed in 97 per cent of the patients who had received either cefuroxime or cefazolin and who met the criteria for evaluation (p = 0.76). Staphylococcus aureus and Staphylococcus epidermidis were the most frequently isolated pathogens. There was no significant difference in the prevalence of wound infections between the patients who had received a one-day regimen of cefuroxime and those who had received a three-day regimen of cefazolin.