Aim To investigate the effect of alprostadil on myocardial perfusion in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods 160 STEMI patients who met the criteria from November 2017 to April 2018 in our hospital were selected as the study subjects. They were randomly divided into alprostadil group (80 cases) and control group (80 cases). Alprostadil group was treated with alprostadil on the basis of routine treatment in the control group. The indexes of myocardial reperfusion, such as thrombolysis in myocardial infarction (TIMI) blood flow grade, corrected TIMI frame count (CTFC), myocardial blush grade (MBG), ST-segment resolution (STR) more than or equal to 50% within 2 hours after PCI and no-reflow after PCI, were compared between the two groups. The levels of inflammatory indexes such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were detected in serum at admission and 7 days after PCI. Left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) of colour sonography were measured at 3 days after PCI and 3 months after discharge. Major adverse cardiac events (MACE) within 3 months after discharge were followed up. Results (1)The baseline data of the two groups were consistent and comparable. (2)The incidences of TIMI grade 3, MBG grade 3 after PCI and STR more than or equal to 50% within 2 hours after PCI in alprostadil group were higher than those in control group (P＜0.05), while the incidence of no-reflow and the number of CTFC frames were lower than those in control group (P＜0.05). (3)There were no significant differences in serum TNF-α, IL-6 and hs-CRP levels between the two groups on admission (P＞0.05). The serum levels of TNF-α, IL-6 and hs-CRP in alprostadil group were lower than those in control group on the 7th days after PCI (P＜0.01). (4)After 3 months follow-up, the LVEDD of the alprostadil group was lower than that of the control group and the LVEF was higher than that of the control group (P＜0.05). The incidences of total MACE and heart failure in the alprostadil group were lower than those in the control group (P＜0.05). Conclusion The application of alprostadil in STEMI patients undergoing primary PCI can effectively reduce inflammation, restore myocardial reperfusion, reduce the occurrence of myocardial microcirculation disorders, and improve cardiac function and prognosis.