AbstractObjectiveResting‐state functional magnetic resonance imaging (rs‐fMRI) at ultra‐high field strengths (≥7T) is known to provide superior signal‐to‐noise to comparable acquisitions at lower field strengths. In this study, we provide a direct comparison of the seizure onset‐zone (SOZ) lateralizing ability of 7T rs‐fMRI and 3T rs‐fMRI.MethodsWe investigated a cohort of 70 patients with temporal lobe epilepsy (TLE). A paired cohort of 19 patients had 3T and 7T rs‐fMRI acquisitions for direct comparison between the two field strengths. Forty‐three patients had only 3T, and eight patients had only 7T rs‐fMRI acquisitions. We quantified the functional connectivity between the hippocampus and other nodes within the default mode network (DMN) using seed‐to‐voxel connectivity, and measured how hippocampal–DMN connectivity could inform SOZ lateralization at 7T and 3T field strengths.ResultsDifferences in hippocampal–DMN connectivity ipsilateral and contralateral to the SOZ were significantly higher at 7T (Cohen's d = 0.51, p = 0.008) than at 3T (Cohen's d = 0.26, p = 0.68) when measured in the same subjects. We found that SOZ lateralization was superior at 7T (receiver‐operating characteristic area under the curve [ROC AUC] = 0.97, 95% confidence interval [CI]: 0.92–1.00) than 3T (ROC AUC = 0.67, 95% CI: 0.36–0.98), for the same subjects scanned at both field strengths. Our findings were reproduced in extended cohorts of subjects scanned at either 3T or 7T. Our rs‐fMRI findings at 7T, but not 3T, are consistent (Spearman ρ = 0.65, p = .01) with clinical fluorodeoxyglucose positron emission tomography (FDG‐PET) lateralizing hypometabolism.SignificanceWe show superior SOZ lateralization in patients with TLE when using 7T relative to 3T rs‐fMRI, supporting the adoption of high field strength functional imaging in the epilepsy presurgical evaluation.