Mohammad Sultan Khuroo, Naira S Khuroo
(1) Background: Hepatitis E remains a major public health challenge in India. (2) Methods: In August 2025, the recombinant HEV 239 vaccine was approved in India for adults aged 18 to 65 years. To establish clinical guidelines tailored to the Indian setting, an expert panel consensus was conducted using a modified Delphi process in accordance with the ACCORD reporting guidelines. (3) Results: A steering committee put forth 18 statements covering vaccine safety, efficacy, and clinical indications, which were independently evaluated by 33 senior Indian hepatologists and epidemiologists. Consensus was assessed using the GRADE framework for level of evidence, balance of benefits and harms, and strength of recommendations. Of the 18 statements, 12 reached the 70% consensus threshold. The panel concluded that the vaccine, which is administered on a standard three-dose schedule, is safe and highly effective in healthy adults, providing protection for up to 10 years. Targeted vaccination was recommended for five high-risk populations: outbreak-affected groups, hyperendemic pockets, women of childbearing age, patients with CLD, and solid organ transplant recipients. Although derived from HEV genotype 1, the vaccine demonstrated cross-protective efficacy against HEV genotype 4. (4) Conclusions: This consensus report provides a framework for deploying the HEV vaccine to mitigate disease burden in India while emphasizing the need for real-world effectiveness and safety data from India.