Objective To investigate the clinical effect of tirofiban combined with clopidogrelin the treatment of patients with acute non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). Methods A total of 70 patients with acute non-ST-elevation myocardial infarction who underwent PCI in our hospital from January 2017 to January 2019 were enrolled and divided into control group and observation group using the envelope method, with 35 patients in each group. The patients in the control group were given clopidogrel alone, and those in the observation group were given tirofiban combined with clopidogrel. Clinical outcome was compared between the two groups. Results Compared with the control group, the observation group had a significantly lower incidence rate of no-reflow in the culprit vessel (2.86% vs 20.0%, P<0.05), a significantly higher incidence rate of grade 3 thrombolysis in myocardial infarction (94.29% vs 48.57%, P<0.05), and a significantly lower incidence rate of adverse cardiovascular events (5.71% vs 25.71%, P<0.05). Compared with the control group, the observation group had a significantly lower maximum platelet aggregation rate at 2 hours after administration(P<0.05). There was no significant difference between the two groups in the incidence rate of bleeding events on day 30 after surgery(P>0.05). Conclusion Inpatients with acute non-ST-elevation myocardial infarction undergoing PCI, tirofiban combined with clopidogrel can reduce no-reflow phenomenon in the culprit vessel and has high safety and clinical value. Therefore, it holds promise for clinical application.