ABSTRACT: Most cancer patients die of non-cancer causes, and peptic ulcer is one cause that deserves attention. To characterize the incidence and risk factors of death from peptic ulcer among cancer patients, we extracted the data of cancer patients registered in the Surveillance Epidemiology and End Results (SEER) program from 1975 to 2016. Out of the 8,471,051 patients extracted from SEER, 4,698 died from peptic ulcer, with a mortality rate of 9.08/100,000 person-years. Meanwhile, the mortality rate in the general population was 5.09/100,000 person-years, giving a standardized mortality ratio (SMR) of 1.78 (95% confidence interval, 1.73-1.84). Patients who are female, of other race, unmarried, and with distant tumor stage have greater SMRs. A higher SMR was associated with a younger age at diagnosis. Among those aged < 40 years at diagnosis, the plurality of fatal peptic ulcers occurred in patients with leukemia and lymphoma, while in patients aged > 40 years, the majority occurred in those with prostate, breast, colorectum, and lung cancer. Patients with upper digestive system malignancies had the highest SMRs and hazard ratios (HRs), which could be ascribed to radiotherapy-induced damage to the gastroduodenum. The risk declined rapidly one year after diagnosis. However, the SMRs in the upper digestive system cancer survivors increased significantly over ten years after diagnosis. Upper digestive system cancers adjacent to the gastroduodenum were associated with higher SMRs and HRs compared with other types of cancer, possibly contributing partially to the damage caused by radiotherapy on the radiosensitive gastroduodenum.