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Purpose: To evaluate the diagnostic values of liver stiffness (LS) measured by 2D-SWE, fibrosis index based on the four factors (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and GGT to PLT ratio (GPR) for assessing liver fibrosis and high-risk esophageal varices (EVs) in patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome. Methods: Data of 141 patients were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. The Spearman correlation coefficient was used for correlation analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic performance. Results: LS and FIB-4 were positively correlated with the fibrosis stage (r = 0.555 and 0.198, respectively). LS had significantly higher areas under the ROC curves (AUROCs) values than FIB-4 for predicting advanced fibrosis (0.818 vs. 0.567, P < 0.001), cirrhosis (0.879 vs. 0.637, P < 0.001), whereas LS and FIB-4 similarly predicted significant fibrosis (0.748 vs. 0.638, P = 0.071) and high-risk EVs (0.731 vs. 0.659, P = 0.303). The optimal cut-off values of 2D-SWE for detecting significant fibrosis, advanced fibrosis, cirrhosis, and high-risk EVs were 8.7 kPa, 12.8 kPa, 14.0 kPa, and 11.0 kPa, respectively. LS values were influenced by fibrosis stage, serum GGT, albumin, and total bilirubin levels. The overall concordance rate of the liver stiffness vs. Scheuer stages was 49.65%. Conclusions: 2D-SWE shows significantly greater diagnostic accuracy than serum fibrosis indexes for diagnosing advanced fibrosis and cirrhosis in patients with AIH-PBC overlap syndrome. [ABSTRACT FROM AUTHOR]