Objective To investigate the clinical efficacy of tirofiban combined with nicorandil on early angina pectoris and its effects on von Willebrand factor (vWF), P-selectin (CD62P), and glycoprotein (GP) Ⅱb/Ⅲa receptor complex levels in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI).Methods This prospective study enrolled 213 AMI patients treated with PCI at Daqing Longnan Hospital from January 2020 to August 2023, randomly assigned to either the observation group (n = 107, receiving intracoronary tirofiban 10 μg/kg plus nicorandil 0.06 mg/kg) or control group (n = 106, receiving tirofiban 10 μg/kg alone). We measured changes in vWF, CD62P, and GPⅡb/Ⅲa levels, recorded angina frequency/duration, assessed severity using the Seattle Angina Questionnaire (SAQ), and monitored adverse events.Results The observation group demonstrated significantly greater reductions in vWF, CD62P, and GPⅡb/Ⅲa levels compared to controls (all P < 0.05). Angina frequency and duration decreased more substantially in the observation group (both P < 0.05). SAQ scores showed greater improvement in physical limitation, angina stability, attack frequency, and treatment satisfaction (all P < 0.05), though disease perception changes were comparable (P > 0.05). Adverse event rates did not differ significantly between groups (P > 0.05).Conclusion The tirofiban-nicorandil combination effectively reduces vWF/CD62P/GPⅡb/Ⅲa levels, decreases angina frequency, and improves symptoms in post-PCI AMI patients, suggesting superior clinical outcomes without increased adverse effects.