In Southern Africa, the African buffalo (Syncerus caffer) is the natural reservoir of foot and mouth disease(FMD). Contacts between this species and cattle are responsible for most of the FMD outbreaks in cattleat the edge of protected areas, which generate huge economic losses. During the late 1980’s and 90’s, theerection of veterinary cordon fences and the regular vaccination of cattle exposed to buffalo contact at theinterface of the Kruger National Park (KNP), proved to be efficient to control and prevent FMD outbreaksin South Africa. However, since 2000, the efficiency of those measures has deteriorated, resulting in anincreased rate of FMD outbreaks in cattle outside KNP, currently occurring more than once a year.Based on retrospective ecological and epidemiological data, we developed a stochastic quantitativemodel to assess the annual risk of FMD virus (FMDV) transmission from buffalo to cattle herds present atthe KNP interface. The model suggests that good immunization of approximately 75% of the cattle pop-ulation combined with a reduction of buffalo/cattle contacts is an efficient combination to reduce FMDVtransmission to one infective event every 5.5 years, emulating the epidemiological situation observed atthe end of the 20th century, before current failure of control measures. The model also indicates that anincreasing number of buffalo present in the KNP and crossing its boundaries, combined with a reductionin the vaccination coverage of cattle herds at the interface, increases 3-fold the risk of transmission (oneinfective event per year).The model proposed makes biological sense and provides a good representationof current knowledge of FMD ecology and epidemiology in Southern Africa which can be used to discusswith stakeholders on different management options to control FMD at the wildlife livestock interface andupdated if new information becomes available. It also suggests that the control of FMD at the KNP inter-face is becoming increasingly challenging and will probably require alternative approaches to controlthis disease and its economic impact.