INTRODUCTION: There is considerable debate surrounding the clinical relevance of an adverse interaction between clopidogrel and proton pump inhibitors (PPIs). Some studies have indicated that PPIs may attenuate the antiplatelet efficacy of clopidogrel, thus leading to increased risk of thrombotic cardiovascular events. AREAS COVERED: From a literature search of MEDLINE and EMBASE, the authors critically appraised data from systematic reviews, randomised controlled trials and observational studies that evaluated platelet function and clinical outcomes in patients receiving concomitant clopidogrel and PPIs. EXPERT OPINION: The evidence from platelet function and cardiovascular outcome studies is highly inconsistent. Higher quality data from randomised trials indicate that use of PPI therapy for up to 6 months is unlikely to cause any adverse interaction with clopidogrel, and there are gastrointestinal benefits with PPI use.