Stroke is a major cause of seizures and epilepsy in adults. Stroke severity, younger age, hemorrhagic subtype of stroke, and alcohol use have been identified as risk factors for the development of stroke-related epilepsy. Despite being a common complication in stroke survivors, current guidelines do not provide strong recommendations about the optimal treatment of post-stroke seizures. No clear guidance is given about the preferred antiseizure medications (ASMs), primary and secondary prophylaxis, and ASMs withdrawal. The management of older patients is further complicated by the presence of comorbidities, pharmacokinetic alterations, and intake of several medications. We present a case of a 77-year-old man affected by epidermolysis bullosa and diabetes mellitus, who suffered from ischemic stroke and then developed post-stroke seizures. This case shows how complex it is to manage post-stroke seizures in an older patient with multiple comorbidities.