Background: Aspirin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) should be highly individualized in order to accurately balance benefits and risks. There are now practical approaches for clinicians to calculate ASCVD and bleeding risks using web-based tools and mobile apps to facilitate good decision making, but their lack of integration with the electronic health record (EHR) and need for extensive data input are barriers to use by busy clinicians. Methods: As part of a clinic randomized trial with 20 primary care clinics, we developed and tested an EHR-integrated Web-based clinical decision support (CDS) system that provided individualized aspirin recommendations to patients and clinicians using risk-benefit calculations. During the 18 month intervention, aspirin recommendations were printed for patients and providers at 75% of eligible encounters. We evaluated the effects of the intervention on rates of appropriate primary prevention aspirin use among 3958 patients with diabetes and 7000 patients without diabetes age 40-75 with uncontrolled CVD risk factors. Results: At baseline, among patients using aspirin, it was not recommended (overused) for 840/1474 (57%) patients with diabetes and 564/1659 (34%) without diabetes. Of patients not using aspirin, it was recommended (underused) by 522/2484 (21%) of patients with diabetes and 4,006/5371 (75%) without diabetes. At the last follow up visit, no significant differences were noted in aspirin use patterns for patients with diabetes. However, among patients without diabetes who were “underusing” aspirin at baseline, 12.9% were using aspirin in CDS clinics compared to 10.4% in control clinics (p=.03). Among patients who were “overusing” aspirin at baseline, 4.1% had discontinued using aspirin in CDS system clinics compared to 7.9% in control clinics (p=.06). Conclusion: Patterns of appropriate aspirin use are different among patients with and without diabetes, with overuse being more common in diabetes and underuse more common in those without diabetes. Our study results suggest that the use of accurate CDS by clinicians and patients improve overall concordance with aspirin. A better understanding of how best to present understandable risk-benefit information to providers and patients is needed.