The development of practice guidelines is an effective way to provide consistent and cost-effective patient care. Despite much progress in developing practice guidelines for various other clinical problems data documenting the efficacy of these guidelines are lacking. The purpose of this study was to compare usage patterns and cost effectiveness of a stress ulcer prophylaxis guideline in a trauma intensive care unit. The trauma intensive care unit team was observed for a 50-day period. Immediately after this period a stress ulcer prophylaxis guideline was implemented, and the team was again observed for a 50-day period. All information was recorded prospectively. The trauma intensive care unit team was blind to the existence of the study. The days of appropriate use of prophylaxis (ulcer prophylaxis prescribed per the practice guidelines) and inappropriate use (use other than per the practice guidelines) in each study phase and the resulting costs were calculated as the primary measurement of outcome. Forty-six patients were studied. The use of practice guidelines in the period after the guideline was implemented of the study reduced overall stress ulcer prophylaxis by 17 per cent (P = 0.04). The appropriate prophylaxis was not significantly different when comparing the two periods of study; however, inappropriate use of prophylaxis (and associated charges) was statistically significantly less frequent after implementation of the practice guidelines. No patients developed clinically important gastrointestinal bleeding. The estimated annual savings of $102,895 in patient charges and $11,333 in actual drug costs in our trauma intensive care unit were due to the implementation of stress ulcer prophylaxis guidelines. We conclude that use of practice guidelines can significantly reduce patient charges without compromising patient care.