Aim:To present a series of medically refractory focal epilepsy patients with multiple or eloquent epileptogenic zones (EZs) in whom a responsive neurostimulation (RNS) system was used as a complementary modality to surgical resection. RNS was also used as a diagnostic tool to monitor long-term epileptogenic activity for enhanced localization, especially in patients with bilateral temporal seizures.Material and Methods:Ten consecutive patients who underwent RNS system placement and surgical resection at a single institution were assessed.Results:The RNS system, with its capacity for chronic ambulatory electrocorticography (ECoG), provided important diagnostic information that helped to modify the plan of surgical resection in one patient with bitemporal epilepsy in order to improve seizure outcomes. In addition, the RNS facilitated the surgical management of patients with multiple or eloquent EZs.Conclusion:The authors report a population of 10 patients in which the RNS system was used as a diagnostic tool for improved localization of EZs over a long interval or as a complementary therapeutic tool in patients with multiple or eloquent EZs.