Purpose <p>Inflammation is associated with the prognosis of patients with coronary artery disease (CAD). However, the joint association of systemic inflammation and the local inflammation index of the coronary artery in adverse prognosis remains unclear.</p> Methods <p>This study included patients who underwent coronary computed tomographic angiography (CCTA) and were diagnosed with CAD. The pericoronary fat attenuation index (pFAI) represents local inflammation in the coronary arteries and is measured from CCTA images. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE). Cox proportional hazards models were used to evaluate the association between systemic inflammation response index (SIRI), pFAI and MACCE, with interaction effects estimated.</p> Results <p>560 participants with CAD (mean age: 67.7 ± 10.7 years; 29.1% female) were enrolled. After a median follow-up of 5.5 years, a total of 90 (16.1%) MACCEs occurred. After fully adjusted, a high level of RCA-pFAI was associated with a higher risk of MACCE (adjusted Hazard Ratio [aHR]: 2.16, 95% confidence intervals [CI]: 1.30–3.58, <i>P</i> = 0.003). Interaction between SIRI and RCA-pFAI was significant (<i>P</i> _interaction = 0.037). The combined increase in both SIRI and RCA-pFAI was associated with higher MACCE risk (aHR: 3.14, 95% CI: 1.55–6.33, <i>P</i> = 0.001 in the pFAI_high/SIRI_high group).</p> Conclusion <p>RCA-pFAI was a risk factor for poor prognosis of CAD patients and had a higher risk stratification value for adverse prognosis when combined with SIRI. Individuals with a high systemic and coronary artery local inflammation state may require more aggressive risk monitoring and intervention.</p> Trial registration <p>The Cardiorenal ImprovemeNt II registry (NCT05050877, 10/09/2021).</p> Graphical abstract <p></p>