Aspirin has been the bedrock of antiplatelet treatment strategies for the secondary prevention of recurrent cardiovascular and cerebrovascular events for the last 3 decades. The limitations of standard aspirin therapy include bleeding, gastrotoxicity, and loss of antiplatelet effect over a 24-hour period in selected high-risk patients. An extended-release (ER) aspirin formulation, Durlaza® (New Haven Pharmaceuticals, Inc., North Haven, CT), has been developed to address some of the latter limitations and may provide an alternative to standard aspirin in the secondary prevention of cardiovascular disease.We searched articles describing the use aspirin for secondary prevention of stroke and cardiovascular events in PubMed published until May 2016. This is a comprehensive review which describes active- and placebo-controlled clinical trials, overview of American and European recommendations, controversies surrounding standard aspirin use, and a description of pharmacodynamics of standard and extended release aspirin formulations. Expert commentary: Available data indicates an increased bleeding risk with the use of standard aspirin therapy in conjunction with potent P2Y12 receptor blockers, and/or oral anticoagulants. Trials evaluating the efficacy of replacing aspirin with a low-dose oral anticoagulant in patients with stable cardiovascular disease or acute coronary syndrome are ongoing. Future studies are warranted to determine if the use of ER-ASA formulation may obviate safety concerns surrounding standard aspirin therapy.