Background Pro‐inflammatory pathways play an important role in the follow‐ups of patients with intracardiac defibrillators (ICDs) for heart failure (HF) reduced with ejection fraction (HFrEF). A newly defined index ‐ the systemic immune‐inflammation index (SII)—has recently been reported to have prognostic value in patients with cardiovascular disease. This study's aim is to evaluate the SII value regarding its association with long‐term mortality and appropriate ICD therapy during a 10‐year follow‐up. Methods This retrospective study included 1011 patients with ICD for HFrEF. The SII was calculated as the neutrophil—to—lymphocyte ratio × total platelet count in the peripheral blood. The study population was divided into two groups according to the SII's optimal cut‐off value to predict long‐term mortality. The long‐term prognostic impact of SII on these patients was evaluated regarding mortality and appropriate ICD therapy. Results The patients with a higher SII (≥1119) had significantly higher long‐term mortality and appropriate ICD therapy rates. After adjustment for all confounding factors, the long‐term mortality rate was 5.1 for a higher SII. (95% CI: 2.9–8.1). The long‐term appropriate ICD therapy rate was 2.0 for a higher SII (95% CI: 1.4–3.0). Conclusion SII may be an independent predictive marker for both long‐term mortality and appropriate ICD therapy in patients with HFrEF.