Background Transcutaneous carbon dioxide tension (PtcCO2) measurement is a promising alternative to arterial carbon dioxide tension (PaCO2) measurement. PaCO2 measurement is invasive and intermittent, whereas PtcCO2 measurement is non-invasive and continuous. However, previous studies evaluating PtcCO2measurements did not include patients undergoing transcatheter aortic valve replacement (TAVR), who experience anticipated hemodynamic changes, particularly before and after valve placement. Therefore, we investigated whether PtcCO2 measurement could provide an alternative to PaCO2 measurement during transfemoral TAVR under monitored anesthesia care (MAC) with local anesthesia. Methodology We conducted a prospective observational study. We included all consecutive patients with severe aortic stenosis who were scheduled to undergo a transfemoral TAVR under MAC at our institution from November 1, 2020, to April 30, 2021. During the procedures, PaCO2 and PtcCO2 were concurrently monitored six times as a reference standard and index test, respectively. PtcCO2 was monitored continuously using a non-invasive earlobe sensor. The agreement between PtcCO2 and PaCO2 measurements was assessed using the Bland-Altman method, and the 95% limits of agreement were calculated. Based on previous studies, we determined that 95% limits of agreement of ±6.0 mmHg would be clinically acceptable to define PtcCO2 as an alternative to PaCO2. Results We obtained 88 measurement pairs from 15 patients. The lower and upper 95% limits of agreement between the PtcCO2 and PaCO2 measurements were -4.22 mmHg and 6.56 mmHg, respectively. Conclusions During TAVR under MAC with local anesthesia, PtcCO2 measurement could not provide a viable alternative to PaCO2 measurement to reduce high PaCO2 events. This study focused on comparing intraoperative periods before and after valve implantation. Therefore, further investigation is warranted to assess the impact of various factors, including the prosthetic valve type and the hemodynamic effects of balloon aortic valvuloplasty, on PtcCO2 measurement in TAVR.