Background: Midterm data comparing clinical outcomes after successful implantation of self-expanding and balloon-expandable transcatheter heart valves (THV) are limited. We aimed to compare 2-year outcomes after successful transcatheter aortic valve implantation (TAVI) with the Edwards balloon-expandable or the Medtronic self-expanding THV. Methods: Two-year outcomes were analyzed according to the implanted THV in the GALILEO trial. Major adverse cardiac and cerebrovascular events (MACCE) was a composite of all-cause death or thromboembolic events including stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism. Results: Among 1644 patients recruited in 136 centers across 16 countries between 2015 and 2018, 499 received a self-expanding and 757 patients received a balloon-expandable THV. Patients treated with a self-expanding THV were more likely to be female, and had higher surgical risk, lower hemoglobin levels, and more frequent valve-in-valve procedures than those with a balloon-expandable THV. After multivariable adjustment, there were no significant differences in major clinical outcomes between self-expanding versus balloon-expandable THV: MACCE (17.0% vs. 13.4%, adjusted-hazard ratios [HR] 1.18, 95% confidence intervals [CI]: 0.82−1.69); all-cause death (11.4% vs. 9.3%, adjusted-HR 1.26; 95% CI: 0.78−2.05); cardiovascular death (8.5% vs. 4.0%, adjusted-HR 1.53; 95% CI: 0.82−2.86), any stroke (5.1% vs. 3.7%, adjusted-HR 0.86; 95% CI: 0.43−1.73); major or life-threatening bleeding (5.9% vs. 6.8%, adjusted-HR 0.93; 95% CI: 0.53−1.63). Clinical Trial Registration: https://www.clinicaltrials.gov. NCT02556203. Conclusions: Two-year follow-up data from the GALILEO trial indicate that successful TAVI either with self-expanding or balloon-expandable THVs according to physician discretion did not show difference in rates of MACCE.