Background <p>Coronary CT angiography (CCTA) derived pericoronary fat attenuation index (FAI) is a reliable quantitative biomarker of vessel inflammation. However, whether this novel index mediated the relationship between metabolic dysfunction–associated fatty liver disease (MAFLD) and major adverse cardiovascular events (MACEs) remains unknown.</p> Methods <p>From January 2019 to December 2022, consecutive patients with stable chest pain who underwent CCTA and unenhanced abdominal CT were prospectively enrolled. All participants were divided into two groups-with MAFLD and without MAFLD according to abdominal CT results. The primary end point was MACEs, defined as cardiac death, nonfatal myocardial infarction, and late revascularization.</p> Results <p>A total of 135 participants with MAFLD and 232 without MAFLD were included in our study. The multivariate logistic regression analysis revealed that MAFLD was significantly associated with obstructive coronary artery disease (OR = 1.86, <i>p</i> = 0.024), high-risk plaque features ≥ 2 (adjusted OR = 2.34, <i>p</i> &lt; 0.001), CT derived fraction flow reserve ≤ 0.8 (adjusted OR = 1.88, <i>p</i> = 0.006), FAI ≥ -70.1HU (adjusted OR = 3.25, <i>p</i> &lt; 0.001) after adjusted for traditional risk factors. Participants with MAFLD showed a lower 36-month MACE-free survival rate than participants without MAFLD (54.0% vs. 83.5%, log-rank <i>p</i> &lt; 0.001). In addition, MAFLD was significantly associated with MACEs (HR = 3.65, 95%CI: 1.83, 7.26, <i>p</i> &lt; 0.001). Furthermore, mediation analysis revealed that FAI mediated 46.8% for the relationship between MAFLD and MACEs.</p> Conclusions <p>MAFLD is associated with CCTA derived plaque characteristics, including geometric, physiologic and inflammatory status. The relationship between MAFLD and MACEs might be partially mediated via coronary inflammation, which could be captured by FAI.</p> Clinical trial number <p>Not applicable.</p>