In the general population, past studies have shown no difference in the beneficial effect of aspirin for primary cardiovascular disease prevention by diabetes status. However, several randomized controlled studies and meta-analyses in adults with diabetes have shown lack of net clinical benefit of aspirin use for primary prevention of ASCVD. The recent ASCEND trial documented cardiovascular benefit of aspirin for primary prevention in adults with diabetes but suggested that the increased risk of bleeding may outweigh the cardiovascular benefit. The decision to initiate aspirin for primary prevention of ASCVD must be considered carefully on an individual basis to balance the cardiovascular benefit and bleeding risk in all patients, especially those with diabetes. A multifactorial approach that focuses on managing ASCVD risk factors such as hypertension, dyslipidemia, dysglycemia, and smoking is recommended in all patients. More research is needed to identify subgroups of people with diabetes who are more likely to benefit from aspirin use for primary prevention of ASCVD and develop better antithrombotic strategies that shift the risk-benefit balance toward an overall net clinical benefit.