Trauma patients are routinely prescribed stress ulcer prophylaxis despite evidence suggesting such therapy be limited to patients with identifiable risk factors for bleeding. With surgeons' consensus, we developed and implemented trauma stress ulcer prophylaxis guidelines, and measured the impact of clinical pharmacists on implementing the guidelines and the effect of the guidelines on drug cost and frequency of major gastrointestinal bleeding. Two groups of 150 consecutive patients admitted with multiple trauma were evaluated before and after guideline implementation and stratified by Injury Severity Score (ISS) to minor (ISS < 9) or moderate to severe (ISS > or = 9) trauma groups. The number of patients prescribed stress ulcer prophylaxis, length and cost of this therapy, and number of patients experiencing major gastrointestinal bleeding (decrease in consecutive hemoglobin > or = 2 g/dl in conjunction with coffee-ground emesis, hematemesis, melena, or hematochezia) were measured. All pharmacist interventions pertaining to stress prophylaxis were collected. Fewer patients were prescribed stress ulcer prophylaxis after guideline implementation (105/150, 70% vs 39/150, 26%, p<0.0001), leading to a decrease in total drug cost of $4558. Use decreased more in patients with minor (40/54, 74% vs 9/59, 15%, p<0.0001) than moderate to severe (65/96, 68% vs 30/91, 33%, p<0.0001) trauma. Neither length of therapy nor agent of choice (> 95% cimetidine) differed between groups. Fifteen (38%) of 38 postguideline prophylaxis orders were determined by the pharmacist not to meet guideline criteria. Recommendations to discontinue therapy were accepted in 9 (60%) of 15 instances. The frequency of major gastrointestinal bleeding remained unchanged between groups (1/150 vs 0/150, p=1.0). Implementation of trauma stress ulcer prophylaxis guidelines limiting therapy to patients with risk factors for bleeding led to a 80% decrease in drug cost and did not affect the frequency of major gastrointestinal bleeding.