Chronic kidney disease (CKD) is a complex disease that may exacerbate the inflammatory state in patients with coronary artery disease (CAD). The predictive value of the Aggregate Index of Systemic Inflammation (AISI) for individuals with CAD and chronic kidney disease (CKD) remains unclear. The data for this study were obtained from the Cardiorenal Improvement II (CIN-II) cohort. Patients ( n = 15,133) with CAD combined with CKD were included. The AISI was calculated using the formula: neutrophil*platelet*monocyte/lymphocyte counts. During a median follow-up of 4.26 years, 3979 deaths occurred, including 2239 cardiovascular (CV) deaths. With adjustment for potential confounding factors, the level of AISI was associated with a higher risk of all-cause mortality (Q [quartile]2, Q3, Q4: hazard ratio [HR] [95 CI%] = 1.20 [1.09–1.32], 1.34 [1.22–1.48], and 1.59 [1.44–1.75], respectively; p trend < 0.001) and CV mortality (Q2, Q3, Q4: HR [95 CI%] = 1.27 [1.11–1.45], 1.50 [1.32–1.71], 1.78 [1.55–2.03], respectively; p trend < 0.001). Elevated AISI level was independently associated with increased risks of all-cause and CV-specific mortality in patients with CAD and CKD.