There is limited evidence to support decision-making regarding discharge antiplatelet therapy after transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the outcome of patients discharged on single-antiplatelet therapy (SAPT) or dual-antiplatelet therapy (DAPT) after TAVI. Consecutive patients were identified by retrospective review of a dedicated TAVI database of a single high-volume center in Milan, Italy, from January 2009 to May 2015. Our primary end point was the rate of net adverse clinical events defined as a composite of all-cause mortality, major bleeding requiring hospitalization, cerebrovascular accidents, redo-TAVI or surgical aortic valve replacement, and valve thrombosis. A total of 439 patients were included in the final analysis; 108 patients were discharged on SAPT and 331 on DAPT. Reasons for discharge SAPT included high risk of bleeding (n = 33; 31%), postprocedural bleeding (n = 42; 39%), thrombocytopenia (n = 20; 18%), vascular complications (n = 13; 12%). The mean length of DAPT was 5.2 ± 2.7 months. Patients discharged in SAPT had a higher incidence of life-threatening bleeding during the index hospitalization. At follow-up, no differences were observed in the incidence of net adverse clinical event, all-cause or cardiovascular mortality, and cerebrovascular events. A similar rate of valve thrombosis was reported in both groups. In conclusion, prescribing only SAPT after TAVI in selected patients was not associated with an increased risk of events and may be an acceptable alternative to DAPT in elderly patients at high risk of bleeding. © 2017 Elsevier Inc.