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Background: Endoscopic ultrasound-guided liver biopsy (EUS-LB) using a 19-gauge (19-G) EUS needle is becoming increasingly popular. We evaluated the efficacy and safety of a 22-G EUS fine needle biopsy (FNB) needle for performing EUS-LB., Methods: Patients referred for evaluation of elevated liver enzymes and without obstructive disease requiring endoscopic retrograde cholangiopancreatography (ERCP) were included. Using a 22-G FNB needle, two passes were made from the left lobe and one from the right. The main outcome measure was adequacy of the specimen for histology interpretation, and the secondary outcome was the safety of EUS-guided liver biopsy with a 22-G FNB needle. Patients were followed for post-procedure complications for 30 days., Results: 40 patients (median age 61 years; 26 women) underwent EUS-LB. Analyzing by needle passes, the median longest core fragment was 12 mm (1st quartile - 3rd quartile 10 mm - 16.25 mm, interquartile range [IQR] 6.25 mm) from the left lobe and 11 mm (10 mm - 15.75 mm, IQR 5.75 mm) from the right lobe. The median cumulative core length per patient was 55 mm (44.5 mm - 68 mm, IQR 23.5 mm). The median cumulative number of complete portal triads (CPTs) per patient was 42 (28.5 - 53, IQR 24.5). The specimen was considered adequate in all 40 patients (100 %). Self-limiting abdominal pain was reported in 6 patients (15 %)., Conclusions: EUS-LB using a 22-G FNB needle is a safe and viable alternative to the use of larger gauge needles, yielding adequate tissue for evaluation of parenchymal disease in 100 % of the patients., Competing Interests: The following authors disclosed financial relationships relevant to this publication. Muhammad K. Hasan is a consultant for Boston Scientific and Olympus America. Robert Hawes is a consultant for Boston Scientific, Olympus America, and Medtronic. Shyam Varadarajulu is a consultant for Boston Scientific and Olympus America. All other authors disclosed no financial relationships relevant to this publication., (© Georg Thieme Verlag KG Stuttgart · New York.)