In the diagnosis of mesial temporal sclerosis (MTS), sensitivity, specificity and predictive values of qualitative assessment using conventional magnetic resonance imaging are low, mainly in mild or bilateral atrophy. Quantitative analysis may improve this performance. We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of quantitative analysis using the hippocampal volumetric index (HVI) and hippocampal asymmetry index (HAI) compared with qualitative assessment in the MTS diagnosis. Twenty-five patients diagnosed with MTS, and 25 healthy subjects underwent conventional magnetic resonance imaging. Hippocampal volumes were obtained using an automated software (FreeSurfer); HVI and HAI were calculated. Receiver operating characteristic curve analysis was performed to obtain the optimal threshold values. Sensitivity, specificity and predictive values were calculated. Sensitivity, specificity, PPV and NPV for qualitative analysis were 44.00%, 96.00%, 91.67% and 63.16%, respectively. In the quantitative analysis, a threshold value of K = 0.22 for HVI provided a sensitivity value of 76.00%, specificity value of 96.00%, PPV of 95.00% and NPV of 80.00%. A threshold value of K = 0.06 for HAI provided the minimum C1 and C2 errors, with a sensitivity value of 88.00%, specificity value of 100%, PPV of 100% and NPV of 89.30%. A statistically significant difference was observed for HAI ( P < 0.0001), and ipsilateral HVI (left MTS, P = 0.0152; right MTS, P < 0.0001), between MTS and healthy groups. The HVI and HAI, both individually and in conjunction, improved the sensitivity, specificity and predictive values of magnetic resonance imaging in the diagnosis of MTS compared to the qualitative analysis and other quantitative techniques. The HAI is highly accurate in the diagnosis of unilateral MTS, whereas the HVI may be better for bilateral MTS cases.