Background The hemoglobin glycation index (HGI) is the difference between measured and estimated glycation of hemoglobin. However, there is limited evidence to investigate the HGI and the clinical outcomes of acute coronary syndrome patients. This study aimed to evaluate the association between HGI and the clinical outcomes of acute coronary syndrome (ACS) in a China cohort. Method This single-center retrospective study was carried out in the Cardiovascular Center of Beijing Friendship Hospital, a total of 11004 consecutive patients with ACS from Dec 2012-Dec 2020 were enrolled in this study. Patients were divided into quintiles according to their HGI levels. The incidence of major adverse cardiac and cerebrovascular events (MACCEs) was recorded. Result HGI were divided into five quintiles quintiles: -0.906 (-7.188, -0.663), -0.491 (-0.663, -0.343), -0.196 (-0.342, -0.039), 0.170 (-0.039, 0.485), and 1.156 (0.485, 7.875), respectively. Competing risk regression revealed that HGI was positively related to all-cause death, CV death, and composite MACCEs. Multivariate Cox proportional hazards regression analysis indicated that hypertension (HR:1.109, P = 0.013), previous stroke (HR:1.208, P < 0.001), past PCI (HR: 1.268, P < 0.001), age (HR: 1.011, P < 0.001), BMI (HR: 0.987, P = 0.012), heart rate (HR: 1.004, P = 0.001), NSTEMI (HR: 1.205, P < 0.001), WBC (HR: 1.020, P = 0.008), eGFR (HR: 0.993, P < 0.001), HDL-C (HR: 0.809, P = 0.002), LVEF (HR:0.240, P < 0.001), LM/three-vessel or proximal LAD involved (HR: 1.208 P < 0.001; HR:0.914, P = 0.019, respectively), and antiplatelet agents during hospitalization (HR:0.806, P = 0.020) independently predicted the incidence of MACCEs in ACS patients. Restricted cubic spline indicated a U-shaped association between the HGI and risk of MACCEs. Conclusion Both low HGI and high HGI was associated with an increased risk of adverse outcomes in patients with acute coronary syndrome, compared with moderate HGI.