Drug-eluting stents (DES) have become a standard treatment for coronary artery disease, but they are associated with a risk of stent thrombosis, which is a serious complication. While DES reduce restenosis compared to bare-metal stents (BMS), they do not necessarily reduce the risk of in-stent thrombosis. Some studies suggest that DES may have a higher risk of thrombosis than BMS, while others indicate no increased risk. Factors contributing to stent thrombosis include procedural issues such as stent malapposition, underexpansion, and multiple stents, as well as patient and lesion characteristics, stent design, and premature discontinuation of antiplatelet drugs. The biological effects of drugs released from DES include activation of signal transduction pathways and inhibition of cell proliferation, which can impair reendothelialization and induce a prothrombogenic environment. Polymers used to load these drugs have also been associated with thrombosis. DES can also impair endothelial function of the coronary artery, potentially increasing the risk of ischemia and occlusion. Although some reports suggest a higher risk of stent thrombosis with DES, the evidence remains inconclusive. Therefore, further clinical trials and mechanistic studies are needed. The pathophysiology of in-stent thrombosis involves various factors, including procedural, patient, and lesion-related factors. Antiplatelet therapy is crucial for preventing thrombosis, and discontinuation of antiplatelet drugs is associated with an increased risk. The thrombogenicity of the stent is influenced by stent materials, strut thickness, and polymer type. Drugs loaded on DES may also have prothrombogenic effects, contributing to a prothrombogenic environment. Additionally, DES may impair reendothelialization, leading to delayed healing and increased thrombogenicity. Risk factors for different time points of DES thrombosis include acute, subacute, late, and very late thrombosis. Acute and subacute thrombosis are associated with primary stenting in acute coronary syndromes, while late and very late thrombosis are linked to discontinuation of antiplatelet therapy. The design of future DES may focus on reducing thrombogenicity through improved coatings and prohealing strategies. Current evidence suggests that DES may have a higher risk of thrombosis compared to BMS, but the benefits of DES in reducing restenosis outweigh the potential increased risk of thrombosis. Further research is needed to fully understand the mechanisms and long-term risks of DES.Drug-eluting stents (DES) have become a standard treatment for coronary artery disease, but they are associated with a risk of stent thrombosis, which is a serious complication. While DES reduce restenosis compared to bare-metal stents (BMS), they do not necessarily reduce the risk of in-stent thrombosis. Some studies suggest that DES may have a higher risk of thrombosis than BMS, while others indicate no increased risk. Factors contributing to stent thrombosis include procedural issues such as stent malapposition, underexpansion, and multiple stents, as well as patient and lesion characteristics, stent design, and premature discontinuation of antiplatelet drugs. The biological effects of drugs released from DES include activation of signal transduction pathways and inhibition of cell proliferation, which can impair reendothelialization and induce a prothrombogenic environment. Polymers used to load these drugs have also been associated with thrombosis. DES can also impair endothelial function of the coronary artery, potentially increasing the risk of ischemia and occlusion. Although some reports suggest a higher risk of stent thrombosis with DES, the evidence remains inconclusive. Therefore, further clinical trials and mechanistic studies are needed. The pathophysiology of in-stent thrombosis involves various factors, including procedural, patient, and lesion-related factors. Antiplatelet therapy is crucial for preventing thrombosis, and discontinuation of antiplatelet drugs is associated with an increased risk. The thrombogenicity of the stent is influenced by stent materials, strut thickness, and polymer type. Drugs loaded on DES may also have prothrombogenic effects, contributing to a prothrombogenic environment. Additionally, DES may impair reendothelialization, leading to delayed healing and increased thrombogenicity. Risk factors for different time points of DES thrombosis include acute, subacute, late, and very late thrombosis. Acute and subacute thrombosis are associated with primary stenting in acute coronary syndromes, while late and very late thrombosis are linked to discontinuation of antiplatelet therapy. The design of future DES may focus on reducing thrombogenicity through improved coatings and prohealing strategies. Current evidence suggests that DES may have a higher risk of thrombosis compared to BMS, but the benefits of DES in reducing restenosis outweigh the potential increased risk of thrombosis. Further research is needed to fully understand the mechanisms and long-term risks of DES.