The systemic inflammatory response index (SIRI) is a novel inflammatory biomarker in many diseases. The aim of this study was to examine the association between SIRI and adverse events in patients with the acute coronary syndrome (ACS) undergoing percutaneous coronary intervention. A total of 1724 patients with ACS enrolled from June 2016 to November 2017 at a single centre were included in this study, and SIRI was calculated for each patient. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall death, non-fatal myocardial infarction, non-fatal stroke, and unplanned repeat revascularization. During a median follow-up of 927 days, 355 patients had MACE. Multivariate Cox analysis showed that SIRI was significantly associated with MACE (hazard ratio: 1.127, 95% confidence interval: 1.034-1.229 p = .007). The results were consistent in multiple sensitivity analyses. The addition of SIRI had an incremental effect on the predictive ability of the Global Registry of Acute Coronary Events risk score for MACE (integrated discrimination improvement: 0.007, p = .040; net reclassification improvement: 0.175, p = .020; likelihood ratio test: p < .001). The restricted cubic spline showed a monotonic increase with a greater SIRI value for MACE (p < .001). SIRI was an independent risk factor for MACE and provided incremental prognostic information in patients with ACS undergoing percutaneous coronary intervention. KEY MESSAGES The SIRI is a strong and independent risk factor for adverse outcomes in patients with ACS undergoing percutaneous coronary intervention. Higher SIRI is associated with a more severe disease status. The SIRI could increase the prognostic value of the GRACE risk score.