Antiplatelet drugs, as the cornerstone of the treatment of coronary heart disease, control the progression of the disease, but bring a higher risk of gastrointestinal bleeding. Relevant guidelines recommend the use of proton pump inhibitors (PPIs) to minimize the risk of gastrointestinal bleeding in patients receiving dual antiplatelet therapy. But for people at low risk of gastrointestinal bleeding, the harms associated with routine use of PPIs may far outweigh the benefits. PPIs increase the risk of lower gastrointestinal bleeding, inhibit the effect of antiplatelet drugs, impair vascular endothelial function, meanwhile induce hypomagnesemia, iron deficiency, vitamins D and K deficiency, etc. Eventually, PPIs may lead to an increase in cardiovascular events. However, the situation is that PPIs are often overused. This review elucidates the mechanisms by which PPIs increase cardiovascular events, thereby reminding clinicians to rationally prescribe PPIs.