Background/Aims: Most countries with high hepatitis B (HB) virus endemicity and most high-income countries have introduced immunization programmes against this infection. However, several low-income countries with intermediate HB endemicity have not done so. We performed a cost-effectiveness analysis of universal childhood HB immunization in such countries using India as an example, since available data on this aspect are limited. Methods: Marginal cost of every life-year and quality-adjusted life-year (QALY) gained with universal HB vaccination was calculated using a Markov model. Two types of analyses (including and excluding expenditure on treatment of long-term complications of HB infection) were done. Several sensitivity analyses and Monte-Carlo simulation were performed. Results: Universal immunization reduced the HB carrier rate by 71%, and increased the number of years and QALY lived by a birth-cohort by 0.173 years (61.072 vs. 60.899 years) and 0.213 years (61.056 vs. 60.843 years), respectively. Marginal costs were US$16.27 per life-year gained and US$13.22 per QALY gained, much lower than annual per capita income. One-way sensitivity analysis and Monte-Carlo simulation confirmed the robustness of the conclusions. Conclusions: Universal HB immunization is highly cost-effective in low-income countries with intermediate endemicity rates.