Background: High performance anti-hepatitis E virus (HEV) IgG assays are crucial for epidemiology. Objective: To evaluate the performance of 2 prototypes developed for the VIDAS (R) automatic system for detecting anti-HEV IgG, one based on the ORF2 antigen (ORF2 prototype) and the other on the ORF2 and ORF3 antigens (ORF2/3 prototype), with reference to the Wantai anti-HEV IgG assay. Study design: The sensitivity of each assay was determined by testing 113 blood samples, 63 from immunocompetent and 50 from immunocompromised patients, with a proven HEV infection defined by detecting HEV RNA. Their specificity was assessed with 103 blood samples that the Wantai assay indicated was negative for anti-HEV IgM and IgG, and negative for HEV-RNA. Cross reactivity was assessed using samples that were positive for hepatitis A virus IgG (n = 16), hepatitis C virus antibodies (n = 15), hepatitis B virus antigen and anti-HBc antibodies (n = 16), rheumatoid factor (n= 14), and negative for anti-HEV IgG with the Wantai assay. Results: The sensitivities in immunocompetent patients were: 95.2% (ORF2), 96.8% (ORF2/3), and 93.6% (Wantai); in immunocompromised patients they were: 66% (ORF2), 72% (ORF2/3), and 68% (Wantai). Both VIDAS prototypes detected low concentrations of anti-HEV IgG. The overall specificity was 100% (ORF2 prototype) and 98.1% (ORF2/3 prototype). Both VIDAS prototypes cross-reacted in five samples (9.6%), mainly those containing HCV antibodies or rheumatoid factor. Conclusion: Both VIDAS (R) prototypes performed very well and appear to be suitable for routine detection of anti-HEV IgG. (C) 2017 Elsevier B.V. All rights reserved.