Aim To investigate the changes of peripheral blood mean platelet volume (MPV), serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) in patients with acute coronary syndrome (ACS) before and after percutaneous coronary intervention (PCI) and their correlation with prognosis. Methods The data of 96 patients with ACS in Geriatrics Hospital of Hainan were retrospectively analyzed. 15 patients with major adverse cardiovascular events (MACE) 6 months after PCI were included in the MACE group, and 81 patients without MACE were included in the non-MACE group. The levels of MPV of peripheral blood, serum VEGF and MMP-9 were compared between the two groups before and after PCI. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of MPV of peripheral blood, serum VEGF and MMP-9 for MACE after PCI in ACS patients. The factors influencing prognosis of ACS patients were discussed. Results The levels of MPV of peripheral blood, serum VEGF and MMP-9 in ACS patients at 3 days and 7 days after PCI were lower than those before PCI (P＜0.05). The above indexes of MACE group before PCI, 3 days and 7 days after PCI were higher than those in non-MACE group (P＜0.05). ROC analysis showed that the area under curve (AUC) of MPV at 7 days after PCI was 0.987, which was larger than those before PCI and 3 days after PCI; When the cut-off value was greater than 11.27 fL, the sensitivity and specificity of MPV in predicting MACE in ACS patients undergoing PCI were 96.67% and 96.20% respectively. The AUC of VEGF was 0.906 at 7 days after PCI; When the cut-off value was greater than 173.80 ng/L, the sensitivity and specificity of VEGF in predicting MACE were 83.33% and 88.61% respectively. The AUC of MMP-9 was 0.843 at 7 days after PCI; When the cut-off value was greater than 334.74 μg/L, the sensitivity and specificity of MMP-9 in predicting MACE were 73.33% and 87.34% respectively. Conclusions The levels of MPV of peripheral blood, serum VEGF and MMP-9 are significantly decreased in ACS patients after PCI. MPV, VEGF and MMP-9 are important risk factors of MACE in ACS patients undergoing PCI, which have high clinical value in predicting MACE.