Background: Inflammation plays a significant role in the pathogenesis of aortic stenosis. This study aimed to investigate the prognostic value of the monocyte-HDL cholesterol ratio (MHR), a new inflammatory marker, in severe aortic stenosis (AS) patients who underwent transcatheter aortic valve replacement (TAVR). Methods: A total of 125 patients with severe AS who underwent TAVR were assessed. Clinical, echocardiographic and laboratory data relevant to the research were retrospectively obtained from the patients’ records. The MHR was determined by dividing the absolute monocyte count by the HDL-C value. The primary endpoints were overall and cardiovascular mortality. Results: During a median follow-up time of 39 months, primary endpoints were developed in 51 (40.8%) patients (overall mortality) and 21 (16.8%) patients (cardiovascular mortality). A receiver operating characteristic (ROC) analysis showed that by using a cut-off level of 16.16, the MHR predicted the all-cause mortality with a sensitivity of 50.9% and specificity of 89.1%. In predicting cardiovascular mortality, the MHR exhibited a sensitivity of 80.9% and specificity of 70.1% when a cut-off level of 13.56 was used. In the multivariate analysis, the MHR (p< 0.0001; 95% CI: 1.06–1.15) and atrial fibrillation (p= 0.018; 95% CI: 1.11–3.38) were found to be significant predictors of overall mortality. Conclusions: This study showed a significant elevation in the MHR among patients who experienced all-cause and cardiovascular mortality and this ratio emerged as an independent predictor of all-cause death in patients with severe AS undergoing TAVR.