BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being used for treatment of severe aortic valve stenosis in patients at intermediate risk for surgical aortic valve replacement (SAVR). Currently, real-world data comparing indications and clinical outcomes of patients at intermediate surgical risk undergoing isolated TAVR with those undergoing SAVR are scarce. METHODS: We compared clinical characteristics and outcomes of patients with intermediate surgical risk (Society of Thoracic Surgeons score 4%–8%) who underwent isolated TAVR or conventional SAVR within the prospective, all-comers German Aortic Valve Registry. RESULTS: A total of 7613 patients at intermediate surgical risk underwent isolated TAVR (n=6469) or SAVR (n=1144) at 92 sites in Germany between 2012 and 2014. Patients treated by TAVR were significantly older (82.5±5.0 versus 76.6±6.7 years, P<0.001) and had higher risk scores (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 21.2±12.3% versus 14.2±9.5%, P<0.001; Society of Thoracic Surgeons score: 5.6±1.1 versus 5.2±1.0, P<0.001). Multivariable analyses revealed that advanced age, coronary artery disease, New York Heart Association class III/IV, pulmonary hypertension, prior cardiac decompensation, elective procedure, arterial occlusive disease, no diabetes mellitus, and a smaller aortic valve area were associated with performing TAVR instead of SAVR (all P<0.001). Unadjusted in-hospital mortality rates were equal for TAVR and SAVR (3.6% versus 3.6%, P=0.976), whereas unadjusted 1-year mortality was significantly higher in patients after TAVR (17.5% versus 10.8%, P<0.001). After propensity score matching, the difference in 1-year mortality between patients with TAVR and SAVR was no longer significant (17.1% versus 15.7%, P=0.59). CONCLUSIONS: Patients at intermediate risk undergoing TAVR differ significantly from those treated with SAVR with regard to age and baseline characteristics. Isolated TAVR and SAVR were associated with an in-hospital mortality rate of 3.6%. In the propensity score analysis, there was no significant difference in 1-year mortality between patients with TAVR and SAVR.