Glucose-6-phosphate dehydrogenase (G6PD) deficiency represents one of the most common erythrocyte enzymopathy. In the era of drug-eluting stents (DESs), the use of prolonged dual antiplatelet therapy (DAPT) with aspirin (ASA) and thienopyridine (clopidogrel or ticlopidine) has become mandatory in the treatment of patients with acute coronary syndromes (ACS) and/or after percutaneous coronary intervention (PCI). However, the use of ASA, and more in general of antiplatelet drugs in patients with G6PD deficiency remains controversial, also for the absence of specific guidelines and scientific evidences. In the present manuscript, we reviewed the few cases available in medical literature, regarding patients with G6PD deficiency treated with percutaneous coronary artery intervention (PCI) and DAPT, with the aim to discuss and clarify the optimal treatment in these patients.