The study assessed the cost-effectiveness of introducing three vaccines – against rotavirus, pneumococcal conjugate and human papillomavirus – in four Pacific island countries (Samoa, Tonga, Tuvalu and Vanuatu). The introduction of all three vaccines could prevent more than 1,000 deaths over the lifetime of the vaccinated groups. Disability-adjusted life-years averted costs ranged from 42% to 73% of per capita gross domestic product at Pan American Health Organization prices, and from 15% to 58% for cheaper vaccines. The impact on immunization budgets would be substantial, ranging from 359% (Samoa) to 1,368% (Vanuatu) of the annual vaccine budget in 2019. The study results show that the introduction of these vaccines could represent good value for money with support from development partners, but financial sustainability requires increasing vaccination budgets and negotiating affordable vaccine prices. The main limitation of the study was the reliance on data from Fiji to report on the disease, as the availability of country-specific data was limited.