AbstractObjectiveHere, we report a retrospective, single‐center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug‐resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking.MethodsFive patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead‐DBS software. Local field potentials recorded over 12–18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in‐clinic broadband LFP recordings, real‐time LFP response to stimulation, and chronic recordings to guide DBS programming.ResultsFour patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose‐dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button‐presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power.SignificanceWe describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real‐time and chronic LFP recording.