Background <p>Achieving timely childhood vaccination is a challenge in low- and middle-income countries (LMICs). A three-month intervention called 10 + 10 + 30 involved 10-minute serial radio drama on vaccination, 10-minute community health worker discussion, and a 30-minute phone-in by listeners was implemented in Jimma Zone, Ethiopia. The goal was to increase childhood vaccination and improve child health outcomes. There is limited evidence of the cost-effectiveness of a radio-only intervention on childhood vaccination in LMICs. Thus, the aim of this study was to examine the cost-effectiveness of 10 + 10 + 30 radio campaign.</p> Methods <p>A scenario modeling design using evidence from a quasi-experimental trial in two districts of Jimma Zone in Ethiopia. The priority populations were all under-five children living in Ethiopia in 2021. The main outcome measures were the proportion of incremental full childhood vaccination coverage, total number of lives saved (mortality avoided), and cost per disability-adjusted life years averted.</p> Results <p>From an estimated unit campaign cost of about US$0.04 per child, we projected a 134% increase in full vaccination coverage, equivalent to an additional 8&#xa0;million fully vaccinated under-five children. If implemented at scale, the intervention had the potential to reduce under-five mortality by about 32%, corresponding to 288,000 lives saved and an estimated cost per averted disability-adjusted life year (DALY) of US$78.</p> Conclusion <p>The study provides evidence to show that a radio vaccination campaign at scale in Ethiopia may have the potential to increase full childhood vaccination coverage, reduce under-five mortality and be cost-effective in terms of averted DALYs.</p> Trial registration <p>This trial was retrospectively registered with ClinicalTrial.gov as NCT04913714 on the 4th of June 2021.</p>