Elective colorectal surgery carries a rate of septic complications of up to 35% in patients not receiving prophylaxis. This can be reduced to 5% in patients receiving appropriate prophylactic agents. The safety and efficacy of cefonicid, a new cephalosporin with a half-life of 4-5 hr, were compared with those of cefoxitin for prophylaxis in patients undergoing elective colorectal procedures or surgery for obstruction of the small bowel. Fifty-seven assessable patients were randomly assigned in a double-blind fashion to therapy with 1 g of cefonicid intravenously (iv) or intramuscularly (im) 1 hr before surgery only or 2 g of cefoxitin iv or im 1 hr before surgery and 2 g every 6 hr for 24 hr. Groups were comparable in terms of underlying diseases. Samples for blood culture were obtained immediately before and after surgery and at 8:00 A.M. on the first and second postoperative days. No blood cultures were positive. Two of 30 patients receiving cefonicid developed wound infections (6%). Two of 27 patients receiving cefoxitin developed wound infections, and one developed an intraabdominal abscess (11%). No significant adverse effects were noted. The results suggest cefonicid may be an effective prophylactic antibiotic for bowel surgery. Most importantly, cefonicid offers the advantages associated with the administration of a single daily dosage, among which are reduction of pharmacy costs and the freeing of nursing hours for patient care.