Rationale Epilepsy is a common, chronic, neurological condition that disproportionately affects individuals living in low- and middle- income countries, including much of sub-Saharan Africa. Epilepsy is treatable, with the majority of individuals who take anti-epileptic drugs experiencing a reduction, or elimination, of seizures. Yet the number of individuals taking and adhering to medication in Africa is low and interventions aimed at improving treatment are lacking. Aims To define the epidemiology of convulsive epilepsy in rural South Africa in terms of incidence, mortality and disability-adjusted life years; to determine outpatient, out-of-pocket costs resulting from epilepsy treatment; to establish the level of adherence to anti-epileptic drugs amongst people with epilepsy; and, to determine whether the introduction of routine visits to people with epilepsy by community health workers is a cost-effective intervention for improving adherence to anti-epileptic drugs. Methods Nested within the Agincourt Health and Demographic Surveillance System, this work utilized a cohort of individuals diagnosed with convulsive epilepsy in 2008 to determine health care utilization and out-of-pocket costs due to care sought for epilepsy. Additionally, using blood samples from the cohort, anti-epileptic drug adherence was measured and, following the cohort, mortality rates were determined. Using these collected epidemiological parameters, disability-adjusted life years due to convulsive epilepsy were determined. Finally, combining the epidemiological and cost parameters, a community health worker intervention was modeled to determine its incremental cost-effectiveness ratio. Key Findings The burden of convulsive epilepsy is lower in rural South Africa than other parts of Africa, likely due to lower levels of known risk factors. Yet the burden, especially in terms of mortality, remains high, as does the treatment gap and health care utilization. Findings from the economic evaluation found the introduction of a community health worker to be highly cost-effective and would likely lower the burden of epilepsy in rural South Africa. Implications Epilepsy contributes to the burden of disease in rural South Africa, with high levels of mortality and a substantial treatment gap. The introduction of a community-health worker is likely to be one cost-effective, community based intervention that would lower the burden of epilepsy by improving adherence to anti-epileptic drugs. Implementing this intervention, based on these findings, is a justified and important next step.