Objective.To test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD).Methods.We used clinically-acquired 3D T1-weighted and 3D FLAIR MRI of 148 patients (median age, 23 years [range, 2-55]; 47% female) with histologically-verified FCD at nine centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed as MRI-negative in 51% of cases, in whom intracranial EEG determined the focus. For risk stratification, the CNN incorporated Bayesian uncertainty estimation as a measure of confidence. To evaluate performance, detection maps were compared to expert FCD manual labels. Sensitivity was tested in an independent cohort of 23 FCD cases (13±10 years). Applying the algorithm to 42 healthy and 89 temporal lobe epilepsy disease controls tested specificity.Results.Overall sensitivity was 93% (137/148 FCD detected) using a leave-one-site-out cross-validation, with an average of six false positives per patient. Sensitivity in MRI-negative FCD was 85%. In 73% of patients, the FCD was among the clusters with the highest confidence; in half it ranked the highest. Sensitivity in the independent cohort was 83% (19/23; average of five false positives per patient). Specificity was 89% in healthy and disease controls.Conclusions.This first multicenter-validated deep learning detection algorithm yields the highest sensitivity to date in MRI-negative FCD. By pairing predictions with risk stratification this classifier may assist clinicians to adjust hypotheses relative to other tests, increasing diagnostic confidence. Moreover, generalizability across age and MRI hardware makes this approach ideal for pre-surgical evaluation of MRI-negative epilepsy.Classification of evidence.This study provides Class III evidence that deep learning on multimodal MRI accurately identifies FCD in epilepsy patients initially diagnosed as MRI-negative.