BACKGROUND: The clinical benefits of percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) are frequently compromised by the occurrence of microvascular obstruction (MVO). The C-reactive protein-triglyceride glucose index (CTI) is a novel biomarker integrating systemic inflammation and insulin resistance. We aimed to evaluate the association between CTI and MVO, as well as its prognostic value for long-term outcomes in AMI patients. METHODS: This study included patients with AMI who underwent successful primary PCI and subsequent cardiac magnetic resonance (CMR). MVO and cardiac function were assessed by CMR. The primary endpoint was the occurrence of MVO, and the secondary endpoint was the incidence of major adverse cardiovascular events (MACE). RESULTS: A total of 967 patients were ultimately included, comprising 255 with diabetes mellitus and 712 without diabetes; 476 patients developed CMR-defined MVO. Higher baseline CTI levels were significantly and independently associated with an increased risk of MVO (OR = 1.33, 95% CI: 1.13-1.56, P = 0.001). A linear dose-response relationship was observed between CTI and MVO risk (P for overall < 0.05, P for nonlinear > 0.05). During a median follow-up of 43 months, higher CTI levels were associated with an increased risk of long-term MACE in the overall population and the non-diabetic subgroup, whereas this association was attenuated in patients with diabetes mellitus. CONCLUSIONS: CTI is independently associated with MVO after PCI in AMI patients and shows modest prognostic value for long-term MACE, particularly in patients without diabetes. As a clinically accessible tool, CTI may facilitate early risk stratification and individualized microvascular protection strategies following PCI.