OBJECTIVE: To analyze the associations between cardiovascular fitness at age 18 years and future risk of epilepsy. METHODS: Population-based cohort study of Swedish male conscripts (n = 1,173,079) born in 1950-1987, who were followed for up to 40 years. Data on cardiovascular fitness were collected during conscription exams and linked with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models controlling for several confounders, including familial factors. RESULTS: Epilepsy was recorded in 6,796 individuals during the follow-up time. In fully adjusted models, low and medium cardiovascular fitness (compared with high) at age 18 years was associated with increased risk of future epilepsy (hazard ratio 1.79, 95% confidence interval 1.57-2.03; and hazard ratio 1.36, 95% confidence interval 1.27-1.45, respectively). The associations changed only marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes. CONCLUSIONS: Low cardiovascular fitness early in life is associated with an increased risk of epilepsy later in adulthood. These results agree with previous results from animal models. We propose that behaviors that increase cardiovascular fitness may act as positive disease-modifiers for the development of epilepsy.