The ideal prophylactic antibiotic regimen has not been established for patients undergoing colectomy, mucosal proctectomy, and endorectal ileoanal anastomosis, a prolonged operation frequently accompanied by abdominal and pelvic contamination and associated with an infection rate up to 20%. The aim of this study was to evaluate, in a prospective, randomized, double-blind fashion, the efficacy of a short perioperative course compared to an extended postoperative course of intravenous antibiotics (cefoxitin) in patients undergoing colectomy with ileoanal anastomosis. Forty patients with ulcerative colitis or familial polyposis coli received a mechanical and oral antibiotic bowel preparation and a standard three-dose perioperative course of intravenous cefoxitin. Patients then were randomized to receive intravenous cefoxitin, 1 g every 6 hours, or placebo for 5 days. No differences in overall postoperative morbidity were observed and neither group developed intra-abdominal, pelvic, or wound infections. It is concluded that a standard three-dose perioperative course of intravenous antibiotics provides adequate prophylaxis in the prevention of infectious complications in patients undergoing colectomy, mucosal proctectomy, and ileoanal anastomosis.