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To determine the impact of histamine2 (H2)-receptor antagonist use on the occurrence of infectious complications in severely injured patients.Some previous studies suggest an increased risk of nosocomial pneumonia associated with the use of H2-receptor blockade in critically ill patients, but other investigations suggest an immune-enhancing effect of H2-receptor antagonists. The purpose of this study was to determine whether H2-receptor antagonist use affects the overall incidence of infectious complications.Patients enrolled in a randomized trial comparing ranitidine with sucralfate for gastritis prophylaxis were examined for all infectious complications during their hospitalization. Data on the occurrence of pneumonia were prospectively collected, and other infectious complications were retrospectively obtained from the medical record. The relative risk of infectious complications associated with ranitidine use and total infectious complications were analyzed.Of 98 patients included, the charts of 96 were available for review. Sucralfate was given to 47, and 49 received ranitidine. Demographic factors were similar between the groups. Ranitidine use was associated with a 1.5-fold increased risk of developing any infectious complication (37 of 47 vs. 26 of 47; 95% confidence interval, 1.04 to 2.28). Infectious complications totaled 128 in the ranitidine-treated group and 50 in the sucralfate-treated group (p = 0.0014). These differences remained after excluding catheter-related infections (p = 0.0042) and secondary bacteremia (p = 0.0046).Ranitidine use in severely injured patients is associated with a statistically significant increase in overall infectious complications when compared with sucralfate. These results indicate that ranitidine should be avoided where possible in the prophylaxis of stress gastritis.