Objective To investigate the effects of freeze-dried recombinant human brain natriuretic peptide (rhBNP) combined with bivalirudin on cardiac function and inflammation in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI).Methods From May 2020 to March 2022, 112 post-PCI ACS patients at our hospital were randomly divided into observation (n = 56, rhBNP+bivalirudin) and control (n = 56, rhBNP+heparin sodium) groups. Cardiac function (LVEF, LVEDD, FS, IVRT), inflammatory markers (MMP-9, NO, ET-1, hs-CRP), adverse events, and event-free survival were compared.Results The observation group showed greater LVEF improvement (P < 0.05) and greater LVEDD reduction (P < 0.05) versus controls. No intergroup differences existed in FS, IVRT, or inflammatory marker changes (all P > 0.05). The observation group had lower adverse event rates (P < 0.05) and longer 1-year cardiovascular event-free survival (P < 0.05).Conclusion rhBNP-bivalirudin combination improves cardiac function with better safety than heparin sodium in post-PCI ACS patients.