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Introduction and Objectives: Transaxillary access (TXA) has become the most widely used alternative to transfemoral access (TFA) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to compare total in-hospital and 30-day mortality in patients included in the Spanish TAVI registry who were treated by TXA or TFA access., Methods: We analyzed data from patients treated with TXA or TFA and who were included in the TAVI Spanish registry. In-hospital and 30-day events were defined according to the recommendations of the Valve Academic Research Consortium. The impact of the access route was evaluated by propensity score matching according to clinical and echocardiogram characteristics., Results: A total of 6603 patients were included; 191 (2.9%) were treated via TXA and 6412 via TFA access. After adjustment (n=113 TXA group and n=3035 TFA group) device success was similar between the 2 groups (94%, TXA vs 95%, TFA; P=.95). However, compared with the TFA group, the TXA group showed a higher rate of acute myocardial infarction (OR, 5.3; 95%CI, 2.0-13.8); P=.001), renal complications (OR, 2.3; 95%CI, 1.3-4.1; P=.003), and pacemaker implantation (OR, 1.6; 95%CI, 1.01-2.6; P=.03). The TXA group also had higher in-hospital and 30-day mortality rates (OR, 2.2; 95%CI, 1.04-4.6; P=.039 and OR, 2.3; 95%CI, 1.2-4.5; P=.01, respectively)., Conclusions: Compared with ATF, TXA is associated with higher total mortality, both in-hospital and at 30 days. Given these results, we believe that TXA should be considered only in those patients who are not suitable candidates for TFA., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)