Immediately before the 2019 American College of Cardiology/American Heart Association Guidelines on Primary Prevention of Cardiovascular Disease, inappropriate use of aspirin or aspirin use without a recommended indication for primary prevention was evident in over one-fourth of patients in this national registry, with significant practice-level variation.

• As per the 2019 American College of Cardiology/American Heart Association Guidelines on Primary Prevention of Cardiovascular Disease, aspirin could be considered for primary prevention (class IIb) in patients 40 to 70 years that are at higher risk of atherosclerotic cardiovascular disease and routine use of aspirin should be avoided (class III:Harm) for patients >70 years.

• Within the National Cardiovascular Disease Registry Practice Innovation and Clinical Excellence Registry, 855,366 patients receiving aspirin for primary prevention were assessed to determine the frequency of patients that would have been considered unindicated or potentially harmful per the recent guideline where aspirin discontinuation may be beneficial.

• Inappropriate use (defined as use of aspirin in patients <40 or >70 years) of aspirin occurred in 27.6% of patients.

• Aspirin use without a recommended indication (defined as aspirin use in patients 40 to 70 years with low, borderline, or intermediate 10-year atherosclerotic cardiovascular disease risk) occurred in 26.0% of patients.

• Significant practice-level variation in inappropriate use was evident.

• These observations aid to ascertain the potential effect of guideline recommendations on contemporary use of aspirin for primary prophylaxis.