Aim To investigate the preventive and therapeutic effects of safflower yellow on acute and subacute in-stent thrombosis (IST) after emergency PCI in advanced age patients with ST-elevated myocardial infarction (STEMI). Methods A total of 786 STEMI patients were enrolled from April 2009 to March 2017, and randomly divided into the study group (388 cases) and the control group (398 cases), the study group was treated with safflower yellow on the basis of routine treatment in the control group. Fasting venous blood were taken to detect platelet activating factor (PAF) in all patients at 1,3, 10 and 30 days after PCI. IST events and hemorrhagic events were monitored within 30 days after PCI.Results Compared with the control group, the study group had a significantly decreased level of the serum PAF at 1,3 and 10 days after PCI. 15 cases (3.9%) occurred acute and subacute IST in the control group and 5 cases (1.3%) occurred acute and subacute IST in the study group, there was significant difference in the incidence of IST between the two groups (χ²＝4.948, P＝0.026). Bleeding events occurred in 5 cases (1.3%) of the study group and 7 cases (1.8%)of the control group, there was no significant difference in the incidence of bleeding events between the two groups (χ²＝0.522, P＝0.770). Conclusion Safflower yellow can prevent the occurrence of acute and subacute IST in advanced age patients with STEMI after emergency PCI and does not significantly increase the bleeding event. Safflower yellow is worth applying in clinical practice furtherly.