The aim of this study was to identify predictors of a resective surgery and subsequent seizure freedom following intracranial EEG (ICEEG) for seizure-onset localization. This is a retrospective chart review of 178 consecutive patients with medically refractory epilepsy who underwent ICEEG monitoring from 2002 to 2015. Univariable and multivariable regression analysis identified independent predictors of resection vs other options. Stepwise Akaike information criteria with the aid of clinical consideration were used to select the best multivariable model for predicting resection and outcome. Discrete time survival analysis was used to analyze the factors predicting seizure-free outcome. Cumulative probability of seizure freedom was analyzed using Kaplan-Meier curves and compared between resection and nonresection groups. Additional univariate analysis was performed on 8 select clinical scenarios commonly encountered during epilepsy surgical evaluations. Multivariable analysis identified the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant as independent predictors of resection (p < 0.0001, area under the receiver operating characteristic curve 0.80, 95% CI 0.73-0.87). Focal ICEEG onset and undergoing a resective surgery predicted absolute seizure freedom at the 5-year follow-up. Patients who underwent resective surgery were more likely to be seizure-free at 5 years compared with continued medical treatment or neuromodulation (60% vs 7%; p < 0.0001, hazard ratio 0.16, 95% CI 0.09-0.28). Even patients thought to have unfavorable predictors (nonlesional MRI or extratemporal lobe hypothesis or dominant hemisphere implant) had ≥50% chance of seizure freedom at 5 years if they underwent resection. Unfavorable predictors, including having nonlesional extratemporal epilepsy, should not deter a thorough presurgical evaluation, including with invasive recordings in many cases. Resective surgery without functional impairment offers the best chance for sustained seizure freedom and should always be considered first. This study provides Class II evidence that the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant are independent predictors of resection. Focal ICEEG onset and undergoing resection are independent predictors of 5-year seizure freedom.