A rapid and reliable diagnostic assay for acute hepatitis E virus (HEV) infection is needed. We evaluated a rapid, immunochromatographic assay for IgM antibodies to HEV (ASSURE HEV IgM Rapid Test) using acute-phase HEV samples (n = 200) from Indonesia and Nepal and convalescent-phase HEV samples (n = 70) from Nepal. Blood donors in Thailand (n = 100), individuals with hepatitis A (n = 80), hepatitis B (n = 45), and hepatitis C (n = 50) in Thailand and Nepal, acute-phase sera of individuals with Epstein-Barr virus infection (n = 20), and rheumatoid factor-positive blood (n = 26) served as negative controls. The assay had a sensitivity of 93% (95% confidence interval [CI] = 88.5-96.1%) and a specificity of 99.7% (95% CI = 98.3-100%). The positive and negative predictive values were 99.5% (95% CI = 97.1-100%) and 95.8% (95% CI = 93.1-97.7%), respectively. These results suggest that this assay is a sensitive and specific tool for the rapid diagnosis of acute HEV infection.