Abstract Background Composite lipid indices have been reported to have associations with several cardiovascular diseases and their negative adverse events. Among these, there are four novel indices that can be easily calculated, namely, triglyceride-glucose index (TyG, calculated from fasting plasma glucose [FPG] and triglyceride [TG]), lipid accumulation product (LAP, calculated from waist circumference [WC] and TG), visceral adiposity index (VAI, calculated from WC, TG, body mass index [BMI], and high-density lipoprotein [HDL]), and atherogenic index of plasma (AIP, calculated from TG and HDL). Herein, we aimed to investigate the impact of these indices on the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods All the patients with ACS who underwent PCI at our institution during the 2015-2022 period were included in the analyses. Patients were divided based on each of the TyG, VAI, LAP, and AIP indices quartiles (Q). The median follow-up was 378 days and the outcome assessed was MACCE composed of all-cause mortality, myocardial infarction, stroke, target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting surgery. Results There was a total of 13,682 patients with ACS undergoing PCI with a mean age of 62.67 ± 11 years and 72.61% male predominance. Regarding the TyG index, patients in Q4 had a higher incidence of MACCE, compared to those in Q1 (adjusted HR [aHR] 1.271, 95% CI 1.067 – 1.513], p-value < 0.01). While in the crude model, patients in Q2, Q3, and Q4 of LAP had significantly higher rates of MACCE, compared to Q1, this association was not observed in the age- and sex-adjusted model and fully-adjusted model. Similarly, there was no difference among the quartiles of VAI and AIP regarding the incidence of MACCE. Kaplan-Meier curves also show that there were significant differences among TyG and LAP quartiles (p-value = 0.0049 and p-value = 0.035, respectively). Conclusion As our findings suggest, patients with higher TyG levels, as a surrogate marker of insulin resistance, had a higher incidence of MACCE. LAP could also play an important role in the incidence of adverse events after PCI. These novel lipid indices could help clinicians in determining the risks of patients with ACS undergoing PCI in order to provide better care to them.Risk of MACCE in different quartilesKaplan Meier Curves for risk of MACCE