This study examines the parameters crucial to cost-effectiveness of universal hepatitis B immunization in India. An incremental cost-effectiveness analysis was done using a decision tree (Markov model) to follow up a hypothetical cohort of 100,000 newborns for the effects of hepatitis B acquired vertically at birth. The measure of effectiveness was disability-adjusted life-years gained. Uncertainty analysis and Scenario analysis were done using Latin hypercube sampling. Hepatitis B endemicity is the most important factor, followed by the cost of vaccine. Other factors of some influence are vaccination coverage, vaccine efficacy, HBeAg positivity, and vaccine wastage.