In a single-center clinical trial, a single 1 gm dose of cefotetan was as effective as a prophylactic agent as multiple 2 gm doses of cefoxitin in the prevention of postoperative infectious morbidity in women undergoing abdominal or vaginal hysterectomy. Among the 39 clinically evaluable women in the cefotetan group and 19 clinically evaluable women in the cefoxitin group, the successful clinical response rates were 97% and 95%, respectively. None of the women in either group who had vaginal hysterectomies developed postoperative complications. One woman in each group developed a major wound infection at the abdominal hysterectomy site. Although the satisfactory bacteriologic response rate was higher among the 36 bacteriologically evaluable women in the cefotetan group than among the 12 bacteriologically evaluable women in the cefoxitin group (83% versus 80%), the difference was not statistically significant. No drug-related adverse reactions were reported for any patient.