Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC.