In Madagascar, dog-mediated rabies has been endemic for over a century, however there is little data on its incidence or impact. We collected data over a 16-month period on provisioning of post-exposure pro-phylaxis (PEP) at a focal clinic in the Moramanga District and determined the rabies status of biting animals using clinical and laboratory diagnosis. We find that animal rabies cases are widespread, and clinic-based triage and investigation are effective ways to increase detection of rabies exposures and to rule out non-cases. A high proportion of rabies-exposed persons from Moramanga sought (84%) and completed PEP (90% of those that initiated PEP), likely reflecting the access and free provisioning of PEP in the district. Current clinic vial sharing practices demonstrate the potential for intradermal administration of PEP in endemic African settings, reducing vaccine use by 50% in comparison to intramuscular administration. A high proportion of PEP demand was attributed to rabies cases, with approximately 20% of PEP administered to probable rabies exposures and an additional 20% to low-to-no risk contacts with confirmed/ probable animal or human cases. Using a simplified decision tree and our data on rabies exposure status and health-seeking behavior, we estimated an annual incidence of 42-110 rabies exposures and 1-3 deaths per 100,000 persons annually. Extrapolating to Madagascar, we estimate an annual burden of 282-745 human rabies deaths with current PEP provisioning averting 1499-3958 deaths each year. Data from other clinics and districts are needed to improve these estimates, particularly given that PEP availability is currently limited to only 31 clinics in the country. A combined strategy of mass dog vaccination , enhanced surveillance, and expanded access to PEP along with more judicious guidelines for administration could effectively reduce and eventually eliminate the burden of rabies in Madagascar.