Aim To evaluate the myocardial level perfusion and clinical outcomes at 6 months of the acute myocardial infarction patients after thrombus aspiration combined with tirofiban and verapamil injection via aspiration catheter compared with thrombus aspiration alone. Methods A total of 281 consecutive patients with acute ST elevation myocardial infarction(STEMI) , who underwent primary percutaneous coronary intervention (PCI) within 24 hours of onset, were assigned to two groups:Group A, intracoronary administration(IC) of a fixed dose of verapamil (200 μg) plus tirofiban (10 μg/kg) after thrombus aspiration and group B, IC administration of heparinized saline 5 mL after thrombus aspiration (n=141 and n=140, respectively). The drugs were selectively injected into the infarct-related artery (IRA) via a thrombus aspiration catheter. The primary end-point was post-procedural corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). The proportion of complete (>50%) ST-segment resolution (STR), the TIMI myocardial perfusion grade (TMPG) 2-3 ratio following PCI, the TIMI flow grade, the incidence of major adverse cardiac events (MACE), the left ventricular ejection fraction (LVEF), the left ventricular end-diastolic diameter (LVEDd) after 6 months of follow-up were observed as the secondary end-points. Results There were no significant differences in the baseline clinical and angiographic characteristics between the two groups. Compared with group B, group A had a lower CTFC (21±6 vs 25±8, P<0.001), a higher proportion of complete STR (66.7% vs 53.6%, P=0.025), an enhanced TMPG 2-3 ratio (65.2% vs 52.1%, P<0.001). There was no statistically significant difference in the final TIMI grade-3 flow between the two groups (91.5 vs 89.3%, P=0.531). The LVEF at 6 months in group A was higher than group B (50±8% vs 46±9%, P<0.001),and the LVEDd in group A was lower than group B (47.6±8.3% vs 52.6±7.7%, P<0.001). However, the incidence of MACE had no statistically difference between the two groups(2.1% vs 3.6%, P=0.712). Conclusions The selective IC administration of a fixed dose of verapamil (200 μg) plus tirofiban via a thrombus aspiration catheter advanced into the IRA after thrombus aspiration is a safe and superior treatment method compared with thrombus aspiration alone in patients with STEMI undergoing primary PCI. This novel therapeutic strategy improves the myocardial level perfusion, in addition to improving heart function. Furthermore, it may improve the postoperative clinical prognosis following PCI.