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To investigate the impact of ulcerogenic drugs on surgery for the treatment of peptic ulcer disease, we reviewed 150 surgical cases. Ulcerogenic drug use (steroids and/or nonsteroidal anti-inflammatory agents, including aspirin) increased from 15% between 1972 and 1977 to 37% between 1983 and 1988. While there was no correlation between ulcerogenic drug use and hemorrhage, obstruction, or intractable pain, 16 (52%) of the 31 perforations and 26 (38%) of the 69 emergency operations were associated with use of ulcerogenic drugs. The overall mortality rate was 11%. Death was correlated with age greater than 65 years and emergency operation, but not with ulcerogenic drug use or other variables. Of 12 patients with histories of peptic ulcer disease who were treated with ulcerogenic drugs without concomitant antiulcer prophylaxis, 11 (92%) required emergency operation to treat perforation or massive hemorrhage. Standard antiulcer medications or misoprostol should be prescribed to elderly patients and to those with histories of ulcers who require ulcerogenic drug therapy.