PurposeAspirin use among patients with diabetes in primary prevention is still a matter of debate. We aimed to evaluate the potential cardiovascular risk benefit of aspirin in primary prevention, using data from a contemporary cohort.MethodsRetrospective analysis of the VITAL cohort with > 20,000 individuals at primary prevention who were followed for a median of 5.3 years. The population was evaluated according to the baseline diabetes status, and then aspirin use was evaluated among diabetic patients. Cox regression models were used to estimate the risks of mortality and cardiovascular outcomes. The estimates were reported using adjusted hazard ratio (HR) and 95% confidence intervals (95%CI).ResultsDiabetic patients (n= 3549; 13.7%) showed to increase the risk of all-cause mortality (HR 1.61, 95%CI 1.33–1.94), and major adverse cardiovascular events (MACE) (HR 1.36 95%CI 1.11–1.68) than non-diabetic population. Diabetic patients taking aspirin were older, more frequently man, hypertensive, current users of statins, and current smokers compared with diabetic patients who did not use aspirin at baseline. There was no difference between diabetic aspirin users and non-users regarding all-cause mortality (HR 0.80, 95%CI 0.59, 1.10), MACE (HR 0.92, 95%CI 0.64, 1.33), coronary heart disease (HR 0.98, 95%CI 0.67, 1.43), or stroke (HR 0.87, 95%CI 0.48, 1.58).ConclusionsThe VITAL data confirmed diabetes as an important risk factor for cardiovascular events in a contemporary cohort but did not show cardiovascular benefits of aspirin in primary prevention among people with diabetes who were shown to be at higher risk of cardiovascular events.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40618-022-02001-3.