Aim To compare procedural outcomes of transcatheter aortic valve replacement (TAVR) patients treated with new-generation valves. Methods We performed a retrospective analysis on an Israeli multicenter registry comprised of four tertiary centers, comparing patient outcomes implanted with the Edwards SAPIEN S3 (ES3) vs. the Medtronic Evolut R (MER) valves. Results The study population included 735 patients (ES3 n  = 223; MER n  = 512). The use of MER was significantly associated ( p  < 0.05) with higher rates of post-dilatation (35% vs. 10%), and the need for a second valve (2.7% vs. 0.5%). Procedural device success was comparable between groups (97% vs. 98%, p  = 0.76); however, moderate angiographic paravalvular leak was higher (3.3% vs. 0.5%, p  = 0.027) for MER vs. ES3, respectively. As compared to MER, 1 month echocardiography revealed higher peak and mean aortic valve gradients for ES3 (12/6 vs. 17/10 mmHg, p  < 0.001, respectively). While the safety outcome at 1 month was lower for MER (8.8% vs. 13.9%, p  = 0.035), similar 1-month, 1-year, and 3-year all-cause mortality were observed (1.9% vs. 1.3%; 8% vs. 8.5%, and 9.7 vs. 10.3%, for MER vs. ES3, respectively). In a propensity score matching analysis, there was no difference in major outcomes between the groups, including device success and the 1 month safety outcome. Conclusion Although favorable efficacy and safety clinical outcomes were observed in this large contemporary registry for both new-generation devices used, some procedural and post-procedural outcomes differ significantly between the two valves.