Abstract: Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes and coronary stent implantation. Patients with CV co-morbidities, receiving antiplatelet agents because of their usefulness in primary or secondary cardiovascular prevention, present a significantly increased GI risk; therefore in those patients gastroprotective agents are useful to reduce this risk. Laboratory studies suggested a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered; those data were corroborated from large retrospective studies.Strong evidence from RCTs and systematic review evaluating the clinical interaction between PPI and clopidogrel failed to demonstrate difference in cardiovascular outcomes, confirming a significant reduction in gastrointestinal bleeding in PPI users.To date, the available evidences do not support the warning that PPI prescription could worsen clinical outcome of patients receiving clopidogrel