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Purpose This study evaluated the effect of epilepsy on the development of hyperlipidemia (HL) in Taiwan. Methods We conducted a nationwide population-based cohort study based on data obtained from the National Health Insurance Research Database of Taiwan. We identified 990 cases involving patients whose epilepsy was newly diagnosed between 2000 and 2005, and we also selected a comparison cohort comprising 3960 patients without epilepsy. Cox proportional hazards regression models were used to examine the association between epilepsy and HL. Results The mean follow-up period was 6.63 years for the epilepsy cohort and 7.49 years for the comparison cohort. The incidence rate of HL was 1.28-fold higher in the epilepsy cohort than it was in the comparison cohort (34.14 vs. 26.96 per 1000 person-years), with an adjusted hazard ratio of 1.17 (95% confidence interval, 1.01–1.36) after adjusting the model to account for the effects of sex and comorbidities. The most at-risk patients were those aged 50 to 59 years (hazard ratio, 1.35; 95% confidence interval, 1.04–1.79). For the epilepsy patients, the combined effect of ischemic heart disease, hypertension, and diabetes was associated with a significantly higher risk of developing HL compared with the patients with neither epilepsy nor any comorbidity. Conclusions Middle-aged epilepsy patients are at a significantly higher risk of developing HL. The results could assist in explaining the high risk of cerebral and cardiac vascular disease in epilepsy patients. [ABSTRACT FROM AUTHOR]