Aim of the study: Frail patients with high grade aortic valve stenosis (AS) undergoing Transcatheter Aortic Valve Implantation (TAVI) have an increased mortality. A connection between frailty and inflammation has been suggested. Monocyte subpopulations are associated with both cardiovascular diseases and chronic inflammatory diseases. This study investigates the association of frailty with monocyte subpopulations and systemic inflammatory parameters in elderly patients undergoing TAVI. Methods: A total of 120 patients with symptomatic AS was examined. Before TAVI implantation, frailty was assessed by a bedside evaluation (eyeball test). In all patients a flow cytometry analysis has been performed. Monocyte subpopulations were defined as follows: classical (CD14⁺⁺CD16⁻), intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14⁺CD16⁺⁺). Expression of CD11b was measured as a marker for monocyte activation. Pro-inflammatory cytokines such as interleukin IL-8, as well as CRP were measured with Cytometric Bead Array or standard laboratory methods. Results: 28 out of 120 patients were frail. These patients showed both, signs of elevated chronic systemic inflammation reflected by elevated CRP (3.7 (1.4–5.4) vs. 5.9 (3.7–29.1), p = 0.001) and an elevated level of intermediate monocytes (37 (24–54) vs. 53 (47–63), p = 0.001). At 6 months after TAVI, 19 of 120 patients died, primarily without relevant dysfunction of the implanted aortic valve. Mortality was significantly higher in the frail as compared with non-frail patients (9 of 28 frail patients vs. 10 of 92 non frail patients, p < 0.001). A binary logistic regression analysis validated frailty and intermediate monocytes as independent predictors for early mortality after TAVI. Conclusion: Chronic systemic inflammation and increased levels of intermediate monocytes are associated with frailty in old patients with severe aortic valve stenosis. Both the syndrome of frailty and elevated intermediate monocytes showed an association with early mortality after TAVI.