Medulloblastomas are one of the most common malignant cancers of the central nervous system in children. Proton beam therapy (PBT) is expected to provide equivalent tumor control to photon therapy while reducing the various adverse events caused by irradiation. Few studies have considered the cost-effectiveness of PBT for pediatric medulloblastoma, considering the multiple adverse effects and reflecting on the latest treatment advancements. A cost-utility analysis of PBT for pediatric medulloblastoma was conducted in a Japanese setting and compared to conventional photon therapy. The analysis was conducted from the public healthcare payer’s perspective, and direct costs for the treatment of radiation therapy and radiation-induced adverse events were included. A Markov model was used, and the health states of secondary cancer, hypothyroidism and hearing loss were defined as adverse events. The time horizon was the lifetime. Incremental cost-effectiveness ratio (ICER) was used as a measurement of cost-effectiveness, with quality-adjusted life years (QALYs) used as an outcome. The costs were estimated from the national fee schedule, and the utility and transition probabilities were estimated from published literature. PBT incurred an additional 1387116 Japanese yen (JPY) and 1.56 QALYs to the comparator. The ICER was JPY 887053/QALY, indicating that PBT was cost-effective, based on the reference value of JPY 5 million/QALY used in the Japanese cost-effectiveness analysis. Deterministic sensitivity analysis showed that the ICER ranged from JPY 284782/QALY to JPY 1918603/QALY as a result of deterministic sensitivity analysis, and probabilistic sensitivity analysis showed that PBT was cost-effective, with a probability of 91.7%.