© 2021 Wiley Periodicals LLCAim: Calcific aortic stenosis (AS) is a common valvular disease especially in elderly population. Inflammation plays significant role in the pathophysiological mechanism. Systemic immune-inflammation index (SII) is a novel marker of immune system and inflammation that includes neutrophil, lymphocyte, and platelet cell counts. The aim of this study was to investigate the predictive value of SII in calcific severe AS. Materials and Methods: Severe calcific AS patients were categorized into two groups: High flow-high gradient (HFHG) AS (n = 289) and low flow-low gradient AS (n = 79). Control group included 273 patients with similar clinical and demographic characteristics but without AS. SII was calculated as absolute platelet count × absolute neutrophil count/absolute lymphocyte count. Results: SII levels were 525 ± 188, 835 ± 402, and 784 ± 348 in control, HFHG AS, and LFLG AS groups, respectively (P <.001). Correlation analyses revealed significant and positive correlation between SII and mean aortic transvalvular pressure gradient (r =.342, P <.001), and negative and significant correlation between SII and AVA (r = −.461, P <.001). Multivariate analysis performed in separate models demonstrated sex, CAD, LDL, and SII levels (Odds ratio [OR]: 1.004, 95 CI%:1.003–1.004) as independent predictors of severe AS in Model 1. According to Model 2, sex, CAD, LDL, and high SII (>661) (OR:5.78, 95 CI%:3.93–4.89) remained as independent predictors of severe AS. Conclusion: SII levels can be useful to predict severe calcific AS patients and significantly correlate with AVA and mean aortic transvalvular pressure gradient.