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Background: Cirrhotic patients are at increased risk of adverse events (AEs) after invasive procedures. However, the safety profile of endoscopic ultrasound (EUS) fine-needle aspiration in cirrhotic patients is still unknown. Objectives: To examine the AEs rate after EUS fine-needle aspiration in cirrhotic patients as compared to a control group of noncirrhotic patients. Methods: Out of 735 patients with suspected abdominal lesions referred to our center between 2006 and 2018, after propensity-score matching, 2 groups were compared: 95 cirrhotics and 95 controls. Primary variables included rate of overall and serious AEs. Secondary endpoint was incidence of acute-on-chronic liver failure. Results: Median age was 64 years, and pancreatic lesions represented the sampled tissue in 57 patients (60%) in each group (p = 1.0) with mean size of 22 mm in both cohorts (p = 0.3). Overall, 20 AEs (21%) of which 9 serious (9.4%) were observed in cirrhotic patients and 3 (3.1%) mild events were experienced by noncirrhotic subjects. Only liver cirrhosis was confirmed as a significant predictor of AEs in multivariate analysis (OR 8.11, 2.34–28; p = 0.001). Overall rate of infections was 6/95 (6.3%), of which 4 were serious (4.2%) in cirrhotics and 1/95 (1%) in the control group (p = 0.05). All serious infections led to the occurrence of acute-on-chronic liver failure. Minor bleeding events were more frequent in cirrhotic patients (4.2 vs. 0%; p = 0.04). Conclusions: The rate of AEs after EUS fine-needle aspiration is higher in cirrhotic patients, and acute-on-chronic liver failure may represent a serious complication of this procedure.