Objective. There is an increased risk of gastrointestinal carcinoma and smoking-related diseases after partial gastrectomy for peptic ulcer disease. The purpose of this study was to evaluate long-term cancer incidence and mortality after parietal cell vagotomy (PCV), a surgical method with a low rate of side effects, but creating hypochlorhydria in the stomach mimicking long-term treatment with antisecretory drugs. Material and methods. Data on 383 ulcer patients operated on with PCV during 1971-80 at Lund University Hospital were compared with the national registers for cause of death and cancer incidence for selected diagnoses. Median follow-up was 28 years and 31 years, respectively. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated. Results. An increased incidence of cancer in the respiratory organs (SIR 1.97, 95% CI: 1.08-3.31) and prostate carcinoma (SIR 1.85, 95% CI: 1.22-2.69) was found, and among men also an increased mortality in prostate carcinoma (SMR 3.85, 95% CI: 1.41-8.38) and chronic respiratory disease (SMR 2.76, 95% CI: 1.01-6.02). Overall mortality was similar to that of the background population and no increased risk of gastrointestinal malignancies was observed. Conclusions. Patients with peptic ulcer operated on with PCV have a long-term increased risk of smoking-related diseases, but PCV does not seem to increase the risk of gastrointestinal carcinoma. An increased risk of, and mortality in prostate carcinoma was found, a cancer previously not found to be related to smoking. This might be the result of surgery-induced hypochlorhydria, which warrants further investigation in patients on long- term proton-pump inhibitors.