Purpose: The purpose of this study is to evaluate whether patients with drug-resistant mesial temporal lobe epilepsy (TLE) due to hippocampal “gliosis only” have different MRI features than those with hippocampal sclerosis (HS). Most TLE patients have HS corresponding to severe neuronal loss and gliosis, but a few have “gliosis only” without significant reduction of neuronal density. Methods: We analyzed the morphology of cerebral 3 T MRIs (T1, T2, and FLAIR) of 103 patients with HS and 20 with “gliosis only” concerning hippocampal and amygdala aspect, volumes, and signal intensity (SI) using Fisher’s exact test, Student’s t test, and principal component analysis. Results: Visually, the ipsilateral hippocampus was hyperintense in both groups, but SI was markedly increased in 74% of HS and in 25% of “gliosis only” patients; the ipsilateral hippocampus was smaller in 92% of HS and in 50% of “gliosis only” patients, and its internal architecture was lost in 57% of HS and 5% of “gliosis only” patients; the contralateral hippocampal SI was altered in 25% of HS and in 70% of “gliosis only” patients (all p < 0.001). Ipsilateral hippocampus of HS patients had lower volume (mean ± SD 2.86 ± 0.87 ml) compared with that of “gliosis only” patients (3.4 ± 1.02 ml) and had higher SI than the contralateral hippocampus of HS patients and then the hippocampus of “gliosis only” patients (all p < 0.01). Conclusion: “Gliosis only” has different MRI hippocampal characteristics than HS: less volume loss, less increase of the T2-w signal intensity, preservation of internal architecture, and more contralateral affection.