OBJECTIVES: The objectives of this study were to: (1) examine the exposure rates to clinically important drug-drug interactions (DDIs) within ambulatory care setting of the Veterans Affairs Medical Centers (VAMCs); and (2) examine the association between the structure of pharmaceutical services within the ambulatory care setting of the VAMCs and DDI exposure rates. METHODS: The study employed an observational, descriptive, cross-sectional design, consisting of a retrospective database analysis of pharmacy records to identify the exposure rate of potential DDIs, and a mailed questionnaire to pharmacy directors to collect information about the characteristics of pharmaceutical services within the ambulatory care setting of VAMCs. The time frame employed to identify DDI exposures was between July 1, 2003 and June 30, 2004. A multivariate regression model was used to assess the association between domains of pharmaceutical services and exposure rates to potential DDIs. RESULTS: Pharmacy records from 2,795,345 veterans who filled prescriptions at 128 VAMCs were analyzed. Overall, the rate of exposure to potential DDIs was 21.54 per 1,000 veterans exposed, ranging from 9.65 to 32.32. Of the 563 ambulatory clinics, 272 (48.3%) had pharmacist coverage. Anticoagulation clinics were the most commonly reported ambulatory clinics, and clinical pharmacy services were most commonly reported in therapeutic drug monitoring clinics. After controlling for the total number of pharmacists on staff, lower rates of potential DDIs were observed in VAMCs with a higher number of specialty ambulatory clinics and lower prescription volumes (p<0.05). CONCLUSION: The study observed wide variation in the rate of exposure to clinically important DDIs within VAMC ambulatory care settings. Lower rates of exposure to potential DDIs were noted in VAMCs with a higher number of specialty ambulatory clinics and lower prescription volumes.