Cefoxitin has been the prophylactic antibiotic of choice for appendectomy and colorectal surgery at this institution. Recent information suggests that cefazolin and metronidazole given as a single intravenous preparation could be a cost-effective alternative to cefoxitin or cefotetan for surgical antimicrobial prophylaxis of uncomplicated appendectomies. This study was conducted to determine the efficacy, toxicity, and cost of the current antibiotic regimens used for prophylaxis of uncomplicated appendectomies, to evaluate the efficacy, toxicity and cost of the cefazolin plus metronidazole combination in uncomplicated appendectomies, and to facilitate a cooperative working relationship between the Departments of Pharmacy and General Surgery. Although the numbers involved were small, this study suggests that the cefazolin/metronidazole combination is cost-effective. It is suggested that research is warranted in evaluating combinations such as this as cost-effective alternatives to current therapy.