BACKGROUND Contrast-enhanced ultrasound (CEUS) is considered a secondary examination compared to computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of hepatocellular carcinoma (HCC), due to the risk of misdiagnosing intrahepatic cholangiocarcinoma (ICC). The introduction of CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS) might overcome this limitation. Even though data from the literature seems promising, its reliability in real-life context has not been well-established yet. AIM To test the accuracy of CEUS LI-RADS for correctly diagnosing HCC and ICC in cirrhosis. METHODS CEUS LI-RADS class was retrospectively assigned to 511 nodules identified in 269 patients suffering from liver cirrhosis. The diagnostic standard for all nodules was either biopsy (102 nodules) or CT/MRI (409 nodules). Common diagnostic accuracy indexes such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for the following associations: CEUS LR-5 and HCC; CEUS LR-4 and 5 merged class and HCC; CEUS LR-M and ICC; and CEUS LR-3 and malignancy. The frequency of malignant lesions in CEUS LR-3 subgroups with different CEUS patterns was also determined. Inter-rater agreement for CEUS LI-RADS class assignment and for major CEUS pattern identification was evaluated. RESULTS CEUS LR-5 predicted HCC with a 67.6% sensitivity, 97.7% specificity, and 99.3% PPV ( P < 0.001). The merging of LR-4 and 5 offered an improved 93.9% sensitivity in HCC diagnosis with a 94.3% specificity and 98.8% PPV ( P < 0.001). CEUS LR-M predicted ICC with a 91.3% sensitivity, 96.7% specificity, and 99.6% NPV ( P < 0.001). CEUS LR-3 predominantly included benign lesions (only 28.8% of malignancies). In this class, the hypo-hypo pattern showed a much higher rate of malignant lesions (73.3%) than the iso-iso pattern (2.6%). Inter-rater agreement between internal raters for CEUS-LR class assignment was almost perfect ( n = 511, k = 0.94, P < 0.001), while the agreement among raters from separate centres was substantial ( n = 50, k = 0.67, P < 0.001). Agreement was stronger for arterial phase hyperenhancement (internal k = 0.86, P < 2.7 × 10 -214 ; external k = 0.8, P < 0.001) than washout (internal k = 0.79, P < 1.6 × 10 -202 ; external k = 0.71, P < 0.001). CONCLUSION CEUS LI-RADS is effective but can be improved by merging LR-4 and 5 to diagnose...