INTRODUCTION A range of somatic and psychiatric disorders occurs frequently in patients with epilepsy (PWE), which adds to the burden of epilepsy. OBJECTIVES To estimate the prevalence and risk factors of somatic comorbidities and analyze the extent of somatic co-medication in adult PWE. PATIENTS AND METHODS This study involved PWE treated in university epilepsy clinic. Data on epilepsy, antiepileptic drugs (AEDs), somatic comorbidities, and their treatment were collected from a structured interview and from medical records. RESULTS The sample population consisted of 636 PWE (mean age 35.3 years); 380 (59.7%) were female and 241 (37.9%) had well-controlled epilepsy. At least one comorbid somatic condition was found in 216 (34%) patients. The most prevalent somatic comorbidities were cardiovascular diseases, allergies, migraine, hyperlipidemia, diseases of the thyroid gland, and chronic lower respiratory diseases. Furthermore, 200 (31.4%) patients were prescribed at least one medication for somatic disorders. Logistic regression analysis revealed several independent risk factors for the occurrence of somatic comorbidities in PWE: older age, shorter duration of epilepsy, lower seizure frequency, and lower number of AEDs. CONCLUSIONS Somatic comorbidities and co-medication with non-AEDs were found in one-third of the relatively young cohort of adult PWE. Patients with pharmacoresistant epilepsy may be at risk of underdiagnosis and undertreatment of somatic comorbidities. The presence of comorbidities may have implications in the diagnosis and treatment of seizure disorder and coexisting condition.