© 2021, Republic of China Society of Cardiology. All rights reserved.Background: There is still no consensus on the treatment of patients with connective tissue disease (CTD) with severe symptomatic aortic stenosis (AS). The aim of this study was to evaluate the feasibility and safety of transcatheter aortic valve implantation (TAVI) in patients with CTD. Methods: Five hundred and fifty consecutive symptomatic severe AS patients who underwent TAVI between 2011 and 2019 were included in this retrospective study, of whom 14 had CTD. Follow-up was performed 30 days, 6 months, and 1 year after the procedure. Results: Of the 14 (2.5%) patients who had CTD, most had rheumatoid arthritis (n = 10), followed by lupus erythematosus (n = 2), scleroderma (n = 1) and mixed (n = 1) CTD. The mean age was 77.6 ± 7.9 years, and there was no statistical difference between the CTD and no-CTD groups. In addition, significantly more of the CTD patients (85.7%) were female compared to the no-CTD group (p = 0.018). None of the patients in the CTD group had acute kidney injury, stroke, major bleeding, or pericardial effusion. However, significantly more patients in the CTD group (n = 4) needed permanent pacemaker implantation than in the no-CTD group (p = 0.008). There were no significant differences between the two groups in terms of mean discharge time (CTD 4.6 ± 2.0, no-CTD 4.5 ± 2.3 days, p = 0.926) and in-hospital mortality [CTD 1 (7.1%), no-CTD 21 (3.9%); p = 0.542]. Conclusions: In this study, we presented the results of TAVI in patients with and without CTD. The TAVI procedure had similar mid-term outcomes in the two groups, and the CTD group had numerically lower rates of major complications at the cost of a higher incidence of pacemaker implantation.