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Simple Summary: Liver transplant is an approach for the curative treatment of early stage hepatocellular carcinoma and the often underlying liver cirrhosis. However, a recurrence of the cancer is to be expected in 10 to 20% of cases after liver transplantation. The treatment of recurrent hepatocellular carcinoma remains difficult, as immunotherapy is usually not recommended for systemic treatment after transplantation. Therefore, it is often necessary to resort to tyrosine kinase inhibitors in advanced stage hepatocellular carcinoma. This multicenter trial aims at assessing the effect of tyrosine kinase inhibitors and immunosuppression on the outcome of patients with recurrent hepatocellular carcinoma after liver transplantation. Introduction: The tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib represent the first-line systemic therapy of choice for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Under sorafenib and lenvatinib, HCC patients have shown increasingly improved overall survival in clinical studies over the years. In contrast, data on overall survival for patients with HCC recurrence after LT under TKIs are scarce and limited to small retrospective series. In this retrospective, multicenter study, we investigated the efficacy of TKI therapy and the influence of immunosuppression in patients with HCC recurrence after LT. Methods: Retrospective data were collected from four transplant centers from Germany and Austria. We included patients with HCC recurrence after LT between 2007 and 2020 who were treated with a TKI. Results: In total, we analyzed data from 46 patients with HCC recurrence after LT. The most common underlying liver disease was hepatitis C, accounting for 52.2%. The median time to relapse was 11.8 months (range 0–117.7 months). The liver graft was affected in 21 patients (45.7%), and 36 patients (78.3%) had extrahepatic metastases at initial diagnosis of recurrence, with the lung being the most commonly affected (n = 25, 54.3%). Of the total, 54.3% (n = 25) of the patients were initially treated locally; 39 (85.8%) and 7 (15.2%) patients received sorafenib and lenvatinib, respectively, as first-line systemic therapy. Median overall survival of the whole cohort was 10.9 months (95% confidence interval (95% CI) 6.9–14.9 months) and median progression free survival was 5.7 months (95% CI 2.0–9.4 months) from treatment initiation. Conclusion: Since history of liver transplantation is considered a contraindication for immunotherapy, prognosis of patients with HCC recurrence after LT remains poor. [ABSTRACT FROM AUTHOR]