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ObjectivePopulation-based studies of epilepsy risk factors are rare. We aimed to evaluate the prevalence of various risk factors associated with new-onset epilepsy after the age of 50 years. We included all incident cases in North Macedonia between 2015 and 2018.MethodsStudy participants were ascertained from the national healthcare platform. We performed a retrospective analysis of Electronic Health Records of 2,367 patients (1,017 females and 1,350 males) whose epileptic seizures started after the age of 50 years. Patients were stratified into 10-year age groups.ResultsThe most common risk factor for new-onset epilepsy in our cohort was stroke, which was associated with new-onset epilepsy in 20% of patients aged 50-59 years and almost 50% of patients aged 70-79 years. The second most frequent risk factor was neoplasm in patients aged 50-69 years and dementia in patients older than 70 years. The other pre-existing conditions included: metabolic disorders, traumatic brain injury, and postencephalitic and inflammatory diseases. Chronic alcoholism was the most common metabolic risk factor associated with new-onset epilepsy and accounted for 84% of cases in this subgroup. Only metabolic disorders were significantly more frequent in males than in females (p<0.00001). We did not identify any epilepsy risk factor in 967 patients (41%). Systemic vascular risk factors were frequent in our cohort: 1,574 patients had hypertension (66%) and 449 patients had diabetes (19%), and 339 had both conditions (14%).SignificanceWe found that structural lesions were the most prevalent risk factor associated with new-onset epilepsy in middle-aged and elderly patients. Recognition of possibly modifiable factors associated with late-onset epilepsy could have a positive impact on reducing the risk of developing epilepsy.