Low dose aspirin, as an anti-platelet medication, has been increasingly prescribed to elderly patients for primary and secondary prevention of cardio- and cerebro-vascular events. Nonetheless, aspirin's effectiveness in such disease prevention is limited by the risk of upper and lower gastrointestinal (GI) complications such as ulceration, hemorrhage and perforation. Aspirin administration is associated with 2-fold increase in the GI risk in middle-aged users without prior history of peptic ulcer and without concomitant medications. However, such GI risk increases dramatically in patients with a prior history of peptic ulcer disease, advanced age, and concomitant use of NSAIDs, corticosteroids, clopidogrel, or anticoagulants. Mechanisms of aspirin-induced GI injury are believed to be through local effects within the GI mucosa that cause topical injury and through systemic inhibition of cyclo-oxygenase (COX) resulting in depletion of mucosal protective prostaglandins. Herein, we focus on the strategy to manage aspirin-induced peptic ulcerations and their complications, based on the scientific evidence.