In appropriate patients oral antiplatelet therapy decreases ischemic risks, but this therapy may increase bleeding complications. Of the major bleeding that occurs, the largest proportion is due to GI hemorrhage. Concomitant use of NSAIDs further raises the risk of GI bleeding. Gastroprotection strategies consist of use of PPIs in patients at high risk of GI bleeding and eradication of H. pylori in patients with a history of ulcers. Communication between cardiologists, gastroenterologists, and primary care physicians is critical to weigh the ischemic and bleeding risks in an individual patient who needs antiplatelet therapy but who is at risk for or develops significant GI bleeding.