313 Background: Orthotopic liver transplantation (OLT) is a potentially curative treatment for hepatocellular carcinoma (HCC). Despite an estimated recurrence rate between 15%-20%, there is currently no proven systemic therapy for the treatment of HCC relapse post OLT. Sorafenib has been a standard therapy for advanced HCC however data is lacking for the safety and efficacy of sorafenib in the setting of concurrent immunosuppressive agents. Methods: A retrospective review was performed of patients who received sorafenib for HCC relapse after OLT. Data on patient characteristics, treatment toxicity and efficacy was collected. The primary objectives were to evaluate toxicity and safety of sorafenib when used in combination with immunosuppressive therapies such as calcineurin and mTOR inhibitors. Secondary objectives were objective response rate, progression free survival (PFS), and time on therapy. Results: 35 patients over the last 11 years received sorafenib for HCC recurrence following OLT. 54.3% of patients received concurrent immunosuppression with tacrolimus. Toxicity from sorafenib was as expected, with no cases of acute or chronic organ rejection whilst on treatment. The median maximum tolerated dose was 400 mg a day with 40% of patients requiring dose reductions. The incidence of any adverse events (AEs) was 88.6%, with 17.1% having Grade 3-4 toxicity. Incidence of Grade 3-4 liver dysfunction was higher than historical studies at 6%. The overall response rate was 2.8% with a median PFS of 2.8 months. Median time on sorafenib was 3.1 months. Conclusions: There is a paucity of evidence guiding treatment of HCC recurrence following OLT. This retrospective review is one of the largest in the literature and shows that sorafenib used concurrently with immunosuppressive therapy for organ transplant is safe, with no precipitation of acute or chronic rejection, although liver function should be monitored closely. The median PFS in our cohort was shorter than expected. The efficacy of other agents should be explored in this population.[Table: see text]