Purpose. Quantification of increased T2-weighted MRI signal that is associated with hippocampal sclerosis (HS) can be performed through (1) mean of hippocampal signal in single-echo T2 MRI and (2) hippocampal T2 relaxometry. It is not clear whether these two techniques are equivalent. In this study, we compare the hippocampal signal, detected by single-echo T2 quantification and by T2 relaxometry, in patients with medial temporal lobe epilepsy (MTLE). Methods. We studied magnetic resonance images from 50 MTLE patients and 15 healthy subjects. We compared the quantification of a T2 signal from single echo images to T2 relaxometry, both obtained from a manually traced region of interest (ROI) in coronal slices involving the whole hippocampus. Repeated measures ANOVA was used to evaluate the differences in the distribution of the Z-scores from single-echo T2 quantification and T2 relaxometry within subjects. Results. We observed a significant difference between the measurements obtained from single-echo T2 quantification and T2 relaxometry (P < .001). Measurements from head, body, and tail of the hippocampus were different (P =.04), with a significant interaction between anatomic location and type of measurement used (P = .008). Post hoc paired comparisons revealed that T2 relaxometry yielded greater Z-scores for the body (P = .002) and tail (P < .0001). Conclusions. For each subject with MTLE, T2 relaxometry was able to detect a higher signal in the body and tail of the hippocampus compared to single-echo T2. This is a possible indicator that T2 relaxometry is more sensitive in detecting T2 abnormalities within the body and tail of the hippocampus in patients with MTLE.163260265