Background. The availability of rotavirus vaccines makes the implementation of a national immunization program an important decision requiring economic considerations. Methods. A cost-benefit analysis of a national rotavirus immunization program in Egypt, from the perspective of the Ministry of Health and Population, and a cost-effectiveness analysis, from a societal perspective, were conducted. Results. For a birth cohort of 1.9 million children, a vaccination program was estimated to prevent 1,140,496 episodes of diarrhea, 438,395 outpatient visits, and 47,508 hospitalizations and to save 2873 lives, resulting in direct Ministry of Health and Population medical savings of $2,481,792 (14,369,578 Egyptian pounds [LE]). On the basis of a $9.18 (53 LE) single-dose cost, rotavirus vaccine introduction would cost the Ministry of Health and Population $34,203,445.87 (198,037,951.56 LE) in health expenditures. This equates to an incremental cost of $30.22 (174.95 LE) per infection prevented. Vaccination would prevent the loss of 94,993 disability-adjusted life-years, resulting in an incremental cost-effectiveness ratio of $363 per disability-adjusted life-year. Conclusions. The introduction of rotavirus vaccine to the national immunization program was not found to be cost saving based strictly from the Ministry of Health and Population perspective; however, the potential benefits of long-term health and economic gains from reduced mortality and morbidity, decreased direct costs of care for families, and indirect societal costs should be considered in such decisions.