AIMS: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) procedures are increasingly used. Specific recommendations on antithrombotic strategies following ViV-TAVR are lacking. We aimed to assess the efficacy of different antithrombotic strategies following ViV-TAVR. METHODS AND RESULTS: We performed a retrospective analysis of German Statutory Health Claims data following ViV-TAVR stratified by antithrombotic strategies according to prescription within 90 days. Antithrombotic regimens included antiplatelet therapy (APT), direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). The composite endpoint was all-cause mortality, stroke and/or systemic embolism (SSE) and mechanical complication of heart valve prosthesis at 12 months. Cox proportional hazard regression models were used to compare outcomes. In total, 908 patients between 2005 and 2022 were identified. Of these, 286 received DOACs, 99 received VKAs, 351 received APT exclusively and 172 had no prescription. The incidence of the composite endpoint was 20.8% in the APT group, 20.3% in the DOAC group and 25.3% in the VKA group which was not statistically significantly different. The rate of SSE in the acetylsalicylic acid (ASA) mono group was higher compared to the dual antiplatelet therapy (DAPT) group (27.3% vs. 12.4%, univariable HR 0.42, 95% CI [0.19, 0.95], p = 0.03). CONCLUSION: In this analysis of German Health Claims data, DOACs seemed to be a safe alternative to VKAs and APT. ASA monotherapy was associated with higher rates of SSE compared to DAPT. Given the high risk of bias of this retrospective analysis and the growing use of valve-in-valve procedures, randomized controlled trials are needed to confirm these findings.