Treatment of 157 patients with perforated duodenal ulcer was evaluated. The condition of the patient dictated that 40 be treated by simple closure. In the remaining patients, vagotomy and drainage and vagotomy and hemigastrectomy were performed in a randomized, prospective study. These patients were observed postoperatively for an average of 4 yr. There was 1 operative death after vagotomy and hemigastrectomy and none after vagotomy and drainage. There were no instances of incapacitating diarrhea in either group, and the frequency of postoperative gastric complaints was essentially the same in both groups. Reoperation was required in 3 patients after vagotomy and drainage and in 1 patient after vagotomy and hemigastrectomy. The anticipated advantage of decreased gastric complaints after vagotomy and drainage compared with their frequency after vagotomy and hemigastrectomy in the definitive treatment of perforated duodenal ulcer was not apparent from this study. To provide protection against further ulcer disease and, at the same time, reduce postoperative gastric sequelae, parietal cell vagotomy without drainage was performed and evaluated in 13 patients with perforated duodenal ulcer. The longest follow-up period of these patients was 2 yr. There was no diarrhea, dumping or other significant gastric complaints. Gastric emptying was normal, and no ulcers have recurred. The results were excellent in 11 patients and good in 2. Early results suggest this method of treatment may be a satisfactory compromise between the use of simple closure that does not protect patients against recurrent ulcer and the use of vagotomy and hemigastrectomy and vagotomy and drainage which impose increased morbidity and death rates on those patients who might not have had further ulcer disease.