<b><i>Introduction:</i></b> Balloon-expandable (BE) and self-expandable (SE) prostheses are the main types of devices currently used in transcatheter aortic valve implantation (TAVI). Despite the different designs, clinical practice guidelines do not make any specific recommendation on the selection of one device over the other. Most operators are trained in using both BE and SE prostheses, but operator experience with each of the two designs might influence patient outcomes. The aim of this study was to compare the immediate and mid-term clinical outcomes during the learning curve in BE versus SE TAVI. <b><i>Methods:</i></b> The transfemoral TAVI procedures performed in a single center between July 2017 and March 2021 were grouped according to the type of implanted prosthesis. The procedures in each group were ordered according to the case sequence number. For each patient, a minimum follow-up time of 12 months was required for inclusion in the analysis. The outcomes of the BE TAVI procedures were compared with the outcomes of the SE TAVI procedures. Clinical endpoints were defined according to the Valve Academic Research Consortium 3 (VARC-3). <b><i>Results:</i></b> The median follow-up time was 28 months. Each device group included 128 patients. In the BE group, case sequence number predicted mid-term all-cause mortality at an optimal cutoff value ≤58 procedures (AUC 0.730; 95% CI: 0.644–0.805; <i>p</i> < 0.001), while in the SE group, the cutoff value was ≤85 procedures (AUC 0.625; 95% CI: 0.535–0.710; <i>p</i> = 0.04). A direct comparison of the AUC showed that case sequence number was equally adequate in predicting mid-term mortality, irrespective of prosthesis type (<i>p</i> = 0.11). A low case sequence number was associated with an increased rate of VARC-3 major cardiac and vascular complications (OR 0.98 95% CI: 0.96–0.99; <i>p</i> = 0.03) in the BE device group, and with an increased rate of post-TAVI aortic regurgitation ≥ grade II (OR 0.98; 95% CI: 0.97–0.99; <i>p</i> = 0.03) in the SE device group. <b><i>Conclusions:</i></b> In transfemoral TAVI, case sequence number influenced mid-term mortality irrespective of prosthesis type, but the learning curve was longer in the case of SE devices.