Introduction To compare endoleak outcomes after thoracic endovascular aneurysm repair (TEVAR) with different stent-graft generations into long-term follow-up. Design retrospective, observational, and single-center cohort study. Methods TEVAR procedures performed between November 1995 and December 2020 were analyzed. The primary endpoint of this study was the freedom from endoleak (type I/III) in four stent-graft generations during the follow-up period. The first generation (GEN1) included: Vanguard; AneuRx and Talent; Stentor; Excluder; Endologix; EndoFit. The second generation (GEN2) included: TAG and TX. The third (GEN3) included: Relay Plus; Valiant Captivia; Zenith Alpha and custom-made. The fourth (GEN4) included: Relay Pro; Conformable C-TAG; Navion; E-Vita; Najuta; Nexus; standard and custom-made thoraco-abdominal devices. Nonaortic and aorta-related survival was considered as secondary outcome. Results A total of 509 TEVAR were included with a 44.3 ± 42.5 months mean follow-up. Freedom from endoleak at 5 years was 65.6%, 61.4%, 76.2%, and 69.1% for GEN1, GEN2, GEN3, and GEN4, respectively ( p = 0.368). The first two generations demonstrated a higher endoleak rate when compared with the two most recent ones (27.2 vs 18.2%, respectively; p = 0.043). GEN1 was an independent risk factor ( p = 0.014) and GEN4 was an independent protective factor ( p = 0.001) for endoleak. GEN1 was found to be a risk factor for type-Ia endoleak ( p = 0.059). GEN4 demonstrated a protective association regarding type-Ib endoleak ( p = 0.012). Overall survival was 75.3%, 44.4%, 27.2%, and 17.6% at 1, 5, 10, and 15 years, respectively. Survival distinguished as non-related versus aortic-related was 86.7% vs 23.5%, 52.7% vs 9.8%, 32.9% vs 2.0%, 21.2% vs 0% at 1, 5, 10, and 15 years, respectively ( p< 0.000). Conclusion Endoleak occurred in a non-negligible percentage of TEVAR patients. A significant reduction of endoleak incidence over evolving stent-grafts generations was registered. Newer stent-graft generations demonstrated better long-term endoleak. Data about long-term outcomes require ongoing updates to prove both the reliability and the durability of newer stent-graft generations.