The aim of the present study was to analyze incidence, risk factors, and association with long-term outcome of postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR). Six hundred and sixty one consecutive patients undergoing TAVR were prospectively enrolled from January 2016 to December 2017. POD was assessed regularly during ICU-stay using the CAM-ICU test. The incidence of POD was 10.0% ( = 66). Patients developing POD were predominantly male (65%), had higher EuroSCORE II (5.4% vs. 3.9%; = 0.041) and were more often considered frail (70% vs. 26%; < 0.001). POD was associated with more peri-procedural complications including vascular complications (19.7 vs. 9.4; = 0.017), bleeding (12.1 vs. 5.4%; = 0.0495); stroke (4.5 vs. 0.7%; = 0.025), respiratory failure requiring ventilation (16.7% vs. 1.8%; < 0.001), and pneumonia (34.8% vs. 7.1%; < 0.001). Consequently, patients with POD had significantly longer ICU- (7.9 vs. 3.2 days < 0.001) and hospital-stay (14.9 vs. 9.0 days; < 0.001), and higher in-hospital mortality (6.1 vs. 2.1%; = 0.017). Logistic regression analysis identified male sex (odds ratio (OR) 2.2 [95% confidence interval (CI) 1.2-4.0); = 0.012], atrial fibrillation [OR 3.0 (CI 1.6-5.6); < 0.001], frailty [OR 4.3 (CI 2.4-7.9); < 0.001], pneumonia [OR 4.4 (CI 2.3-8.7); < 0.001], stroke [OR 7.0 (CI 1.2-41.6); = 0.031], vascular complication [OR 2.9 (CI 1.3-6.3); = 0.007], and general anesthesia [OR 2.0 (CI 1.0-3.7); = 0.039] as independent predictors of POD. On Cox proportional hazard analysis POD emerged as a significant predictor of 2-year mortality [HR 1.89 (CI 1.06-3.36); = 0.030]. POD is a frequent finding after TAVR and is significantly associated with reduced 2-year survival. Predictors of delirium include not only peri-procedural parameters like stroke, pneumonia, vascular complications and general anesthesia but also baseline characteristics as male sex, atrial fibrillation and frailty.