Foot-and-mouth disease (FMD) is arguably the most damaging animal disease, affecting three-quarters of the global livestock population. This paper provides a cost-benefit analysis of the first five-year program that used vaccination to contain and control FMD in an endemic country, Vietnam. Our spatial and dynamic model to simulate FMD outbreaks fully considered the distance among livestock premises, their herd sizes, and composition, all of which significantly affect FMD transmission. Our program benefit was consistently estimated due to the Law of Large Number and the design of pairing the control and treatment scenarios which allowed capturing the true benefit of each outbreak realization. The data used to monetize the program benefit were largely drawn from Vietnam's context and statistics, thus obviating the need to make many potentially undue assumptions. Meanwhile, the program costs were actual spending and allocated budget. We found that the vaccination program is highly cost-effective for Vietnam, yielding a net present value of US$136 million (in 2006 prices) over five years and a benefit-cost ratio of 5.7. Our results were robust to different assumptions about the vaccine effectiveness of the livestock unit.