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Background: Little is known about longitudinal prescribing practices for anti-epileptic drugs (AEDs) in South Africa. The prescribing patterns and associated direct medicine costs of AEDs in the private health sector were investigated, using claims data from January 1, 2008 to December 31, 2013. Methods: The annual prevalence of prescriptions, AEDs and AED generics per patient with epilepsy (ICD-10 code G40) was determined. Cost analyses conducted included the calculation of the total direct cost of AEDs (medical scheme contribution, patient co-payment, and single exit price (SEP)), and the average cost per AED per year. Results: Prevalence of patients claiming anti-epileptics ranged between 0.87% and 0.91% from 2008 to 2013. AED prescriptions/ patient ranged from 11.76 (95% CI, 11.56–11.95)] in 2008 to 11.90 (95% CI, 11.71–12.09) in 2013. Patients aged 40–65 years had the highest number of AED prescriptions/year. Valproate was most prescribed, followed by lamotrigine and carbamazepine. Average cost per AED increased from R237.12 (95% CI, 233.58–240.65) in 2008 to R522.32 (95% CI, 515.24–529.41) in 2013, while the average patient co-payments increased from R27.76 (95% CI, 26.63–28.89) to R264.32 (95% CI, 260.61–268.03). Prescribing of generics increased by 12.84%. Conclusions: Generic prescribing increased over time; however, patient co-payments increased dramatically