Approximately 1% of the U. S. population suffers from epilepsy. Among these patients, 30% are defined as medically intractable and thus potential candidates for epilepsy surgery, most commonly amygdalohippocampectomy (AH) with or without anterior temporal lobectomy (ATL) in temporal lobe epilepsy (TLE). Approximately 65% of patients treated with AH will be seizure-free. Therefore, there is need to improve prognostic value of selection criteria for AH surgical candidates. Thus, we pursue an approach known as neurosurgical genomics, where the identification of RNA-Seg biomarkers will establish gene expression profiles in patients with different seizure outcomes. Whole transcriptome analyses were performed to test the hypothesis that hippocampal tissue RNA expression differs between patients rendered seizure-free (SF) and non-seizure-free (NSF) to establish predictive prognostic biomarkers. A total of 14 patients (mean age: 33.1 years, range 16-56 years; 10 males, 4 females) with intractable TLE have undergone AH/ATL with 1-year minimum follow-up dichotomized into SF and NSF. Logistic regression analysis of Next Generation Sequencing reveals sufficient statistical power for hippocampal RNA expression data.