BACKGROUND AND AIM: To evaluate if spleen stiffness measurement (SSM) can rule out the presence of high-risk varices in patients with cirrhosis, avoiding an upper gastrointestinal endoscopy (UGE). METHODS: We enrolled 71 cirrhotic patients irrespective of liver disease\'s etiology. 2D shear wave elastography (SWE) of spleen and UGE was performed. High-risk varices (HRV) were defined as esophageal varices >/= 5 mm and/or red spots and any gastric varices. RESULTS: Esophageal varices were documented in 37 (52.1%) and HRV in 25 (35.2%) patients. SSM was not technically feasible in 7/71 patients (9.8%). From the remaining 64 patients, when those with cholestatic liver disease were excluded (n = 17), SSM < 35.8 kPa was found to exclude well the existence of HRV offering an AUROC of 0.854 (p < 0.001), sensitivity 88.9%, negative predictive value (NPV) 91.3%, specificity 72.4%, and positive predictive value (PPV) 66.7%. Only 2/47 patients (4.3%) were misclassified, and 23 (48.9%) could avoid endoscopy. In the total cohort of 64 patients, SSM < 33.7 kPa was found to exclude well the presence of HRV offering AUROC 0.792 (p < 0.001), sensitivity 91.7%, specificity 60%, NPV 92.3%, and PPV 57.9%. The misclassification rate was 3.1% (2/64), while 26/64 (40.6%) could avoid endoscopy. CONCLUSIONS: 2D-SWE of spleen is a reliable method for ruling out the presence of HRV in cirrhotic patients. If larger studies confirm our results, a large number of endoscopies could be avoided.