INTRODUCTION: Rotavirus vaccines have the potential to prevent a substantial amount of life-threatening gastroenteritis in young African children. This paper presents the results of prospective cost-effectiveness analyses for rotavirus vaccine introduction for Kenya and Uganda. METHODOLOGY: In each country, a national consultant worked with a national technical working group to identify appropriate data and validate study results. Secondary data on demographics, disease burden, health utilization, and costs were used to populate the TRIVAC cost-effectiveness model. The baseline analysis assumed an initial vaccine price of $0.20 per dose, corresponding to Gavi, the Vaccine Alliance stipulated copay for low-income countries. The incremental cost-effectiveness of a 2-dose rotavirus vaccination schedule was evaluated for 20 successive birth cohorts from the government perspective in both countries, and from the societal perspective in Uganda. RESULTS: Between 2014 and 2033, rotavirus vaccination can avert approximately 60,935 and 216,454 undiscounted deaths and hospital admissions respectively in children under 5 years in Kenya. In Uganda, the respective number of undiscounted deaths and hospital admission averted is 70,236 and 329,779 between 2016 and 2035. Over the 20-year period, the discounted vaccine program costs are around US$ 80 million in Kenya and US$ 60 million in Uganda. Discounted government health service costs avoided are US$ 30 million in Kenya and US$ 10 million in Uganda (or US$ 18 million including household costs). The cost per disability-adjusted life-year (DALY) averted from a government perspective is US$ 38 in Kenya and US$ 34 in Uganda (US$ 29 from a societal perspective). CONCLUSIONS: Rotavirus vaccine introduction is highly cost-effective in both countries in a range of plausible 'what-if' scenarios. The involvement of national experts improves the quality of data used, is likely to increase acceptability of the results in decision-making, and can contribute to strengthened national capacity to undertake economic evaluations.