Background: Vaccinating girls against human papillomavirus (HPV) infection is a highly effective and cost-effective intervention to provide protection against HPV-induced cancers. Since vaccination coverage rates among girls is modest in the Netherlands, additional strategies should be implemented to improve the protection against HPV-related cancer. Here we assessed the benefits and cost-effectiveness of gender-neutral vaccination. Methods: We designed a static Markov model with a lifelong time horizon to simulate a cohort of 100,000 12-year-old Dutch boys. The model compares health and economic effects of HPV vaccination taking the current female vaccination coverage into consideration. HPV prevalence in boys was corrected for the predicted herd effects of the female programme in 2017. We extracted transition probabilities from peer-reviewed literature and previously constructed models. The robustness of the model was tested with multiple sensitivity analyses. Results: Vaccinating 30% of 100,000 12-year-old boys prevents 18, 13 and 25 cases of anal, penile, and oropharyngeal cancers in men, respectively. A total of 205 quality-adjusted life-years (QALYs) are saved by preventing cancer-related morbidity and mortality. Assuming a vaccine price of (sic)50 per dose, the incremental cost-effectiveness ratio (ICER) is (sic)17,907 per QALY. In addition, due to vaccine-induced herd effects, we estimated that 110 cases of cancer in females would be additionally prevented and 246 QALYs would be gained in the female cohort, bringing the total to 166 cancers prevented and 451 QALYs gained. Taking these additional benefits of boys' vaccination into account, the overall ICER was estimated at (sic)7310 per QALY gained. The model outcomes are most sensitive to variation in vaccine price, herd immunity from females and vaccine efficacy. Conclusions: Vaccination of boys, additional to girls, will prevent a relevant number of cancers in both boys and girls. Based on the current Dutch situation vaccination of HPV in boys is ...