OBJECTIVE: Coronary heart disease (CHD) is the most common cause of mortality and morbidity. Acute coronary syndrome (ACS) is the most advanced form of the CHD spectrum. The triglyceride-glucose index (TGI) and atherogenic plasma index (AIP) are associated with future cardiovascular events. This study investigated the association of these parameters with the severity of CAD and prognosis in the first-diagnosed ACS patients. PATIENTS AND METHODS: Our study was designed retrospectively, including 558 patients. Patients were divided into four subgroups: high and low TGI and high and low AIP. SYNTAX scores, in-hospital mortality, major adverse cardiac events (MACE), and survival were compared at 12-month follow-up. RESULTS: More three-vessel disease and higher SYNTAX scores have been detected in the high AIP and TGI groups. More MACEs have been observed in high AIP and TGI groups than low groups. AIP and TGI were found to be independent predictors for SYNTAX ≥23. While AIP has been found to be an independent risk factor for MACE, TGI has not been detected as an independent risk factor. In addition to AIP, age, three-vessel disease, and lower EF were the independent risk factors for MACE. Survival was lower in high TGP and AIP groups. CONCLUSIONS: AIP and TGI are costless bedside parameters that can be easily calculated. These parameters can predict the severity of CAD in first-diagnosed ACS patients. Besides, AIP is an independent risk factor for MACE. AIP and TGI parameters can guide our treatment in this patient population.