With the advances in coronary interventional devices, especially the use of drug-eluting stents, PCI of the left main stem is no longer off-limits, and the 2005 PCI guidelines place intervention of the left main stem in category IIb indications. In real clinical practice, some patients with more comorbidities, such as renal insufficiency and chronic obstructive pulmonary disease, are at particularly high risk for surgical CABG, when patients have no choice but to undergo PCI. There are now many centers in China that perform unprotected left main stem (ULMCA) PCI. Left main stem PCI is a challenge to the interventional skills of the operator, requiring skill and a good psychological profile, however, it should be emphasized that successful PCI is only part of the treatment, and postoperative antithrombotic therapy is as important as the interventional operation itself. The left main stem has a special anatomical location, and the blood supply to the left main stem accounts for the entire left ventricular blood supply; therefore, acute occlusion of the unprotected left main stem often results in sudden cardiac death, making it difficult for the patient to be resuscitated. Currently, drug-coated stents (DES) are mainly used for left main stem PCI, and the coating drugs include rapamycin and paclitaxel. While these coating drugs inhibit smooth muscle cell migration and endothelial proliferation and reduce the rate of in-stent restenosis, they also inhibit and slow down the process of vascular endothelialization. Angioscopy and autopsy have found that the endothelial healing time of DES is prolonged up to more than 1 year, and endothelialization is still not seen even at 40 months, and the vascular endothelium is a critical barrier to prevent thrombus formation; therefore, delayed stenting after DES placement has been reported The incidence of thrombosis was increased compared with that of metallic bare stents. For the left main stem, in-stent thrombosis is very aggressive and can quickly cause circulatory collapse and sudden death in patients, so antithrombotic therapy after left main stem stenting is crucial. In addition, in left main stem lesions, 1/3 of which have accumulated terminal bifurcations, overlapping of multiple stent beams and poor stent apposition may occur if the bifurcated stent procedure is used, and in individual patients there may be entrapment that is not detected by imaging, and in these cases, postoperative antithrombotic therapy is even more critical. Antithrombotic therapy after left main stem stenting has both commonalities and specificities with antithrombotic therapy of stents in other sites. The commonality lies in the use of antiplatelet agents and anticoagulant drugs, but the specificity is reflected in the word “intensification”, which contains at least two meanings: first, the intensity should be large enough, and second, the duration should be long enough. However, due to individual differences, some patients are not sensitive to these two antiplatelet drugs, which is also known as “aspirin resistance” and “clopidogrel resistance”. However, due to individual differences, some patients are not sensitive to these two antiplatelet drugs, which is called “aspirin resistance” and “clopidogrel resistance”, and these patients are not uncommon in clinical practice. Obviously, conventional antiplatelet therapy is not sufficient for this group of patients, whose risk of developing stent thrombosis is greatly increased. Therefore, it is necessary to test platelet function in patients with DES placement, which is an important guide for individualized antiplatelet therapy. However, platelet aggregation force testing is not routinely performed in many centers in China, which would expose many patients with antiplatelet drug resistance to the risk of stent thrombosis. At our center, we routinely test adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation after patients undergo PCI, and add triple antiplatelet therapy, i.e., aspirin + clopidogrel + cilostazol (PEDA), or anticoagulation, i.e., aspirin + clopidogrel + warfarin, for patients with ADP-induced platelet inhibition of less than 50%, to keep INR control between 2.0 and 2.5, while avoiding complications such as neurological or gastrointestinal bleeding. Such patients should also have long-term outpatient clinical follow-up to monitor the inhibition of platelet function and the intensity of anticoagulation. The second issue is the time course of antiplatelet therapy. The ACC/AHA and ESC guidelines do not yet provide a clear answer to the question of how long dual antiplatelet therapy should be continued after drug-eluting stent placement. However, based on concerns about stent thrombotic events, particularly the increased reporting of stent thrombotic events due to premature discontinuation of antiplatelet agents, the 2007 ACC/AHA PCI guideline update has clearly stated that dual antiplatelet therapy should be administered for at least 12 months after DES placement in patients who are not at high risk for bleeding tendencies, but there is no specific emphasis in the new guideline update for left main stem stents. In clinical practice, the special anatomic location of the left main stem and the increased risk of late thrombosis due to DES make the issue of antiplatelet time course not something to be taken lightly. There are case reports of in-stent thrombosis 28 months after left main stem drug-eluting stent placement. Therefore, the duration of antithrombotic therapy after left main stem drug stent placement is very important, and in our center’s experience, for those patients without bleeding tendency but at risk of stent thrombosis, such as renal insufficiency and diabetes mellitus, or patients with overlapping left main stem stents and left main stem bifurcation stents, we can consider extended or even lifelong antiplatelet therapy in a double combination. In addition, it should be emphasized that for patients with left main stem stents, clinical and coronary angiographic follow-up should be intensified, and coronary angiography should be performed 9 to 12 months after surgery, and if available, intravascular ultrasound or optical coherence tomography (OCT) can be performed to evaluate the effect of left main stem stenting, the endothelial coverage of the vessel, and to provide a basis for adjustment of drug therapy. In conclusion, antithrombotic therapy for left main stem PCI must be individualized according to the patient’s clinical characteristics, interventional operations and laboratory findings. As a clinician, the importance of dual antiplatelet therapy should be repeatedly emphasized to the patient, and the dose should not be reduced or discontinued at will to avoid the disastrous consequences of stent thrombosis after discontinuation of antiplatelet drugs. Only in this way can the risk of stent thrombosis be minimized.