PURPOSE Our aim was to evaluate the safety and efficacy of electrical stimulation of the hippocampus in a long-term follow-up study, as well as its impact on memory performance in the treatment of patients with refractory mesial temporal lobe epilepsy. METHODS Nine patients were included. All had refractory partial complex seizures, some with secondary generalizations. All patients had a 3-month-baseline-seizure count, after which they underwent bilateral hippocampal diagnostic electrode implantation to establish focus laterality and location. Three patients had bilateral, and six, unilateral foci. Diagnostic electrodes were explanted and definitive Medtronic electrodes were implanted directed into the hippocampal foci. Position was confirmed with MRI and afterwards, the deep brain stimulation system internalized. Patients signed the informed consent approved by the Hospital's Ethics Committee and began a double-blind stimulation protocol. Patients attended a medical appointment every 3 months for seizure diary collection, deep brain stimulation system checkup, and neuropsychological testing. RESULTS Follow-up ranged from 18 months to 7 years. Patients were divided in two groups: five had normal MRIs and seizure reduction of >95%, while four had hippocampal sclerosis and seizure reduction of 50-70%. No patient had neuropsychological deterioration, nor did any patient show side effects. Three patients were explanted after 2 years due to skin erosion in the trajectory of the system. CONCLUSIONS Electrical stimulation of the hippocampus provides a nonlesional method that improves seizure outcome without memory deterioration in patients with hippocampal epileptic foci.