Background and objectives:The purpose of the study was to seek a relationship between drug-resistant epilepsy and structural alterations in neuroimaging to strengthen the link between the clinical and surgical management. A second objective was to determine an association between drug-resistant epilepsy and subject gender, the age of first seizure, and the type of seizure. Materials and methods: Over 632 medical records were scrutinized in search of those satisfying the inclusion criteria to end up with a sample of 108 subjects. Neuroimaging specialists reviewed each of the magnetic resonance imaging (MRI) studies looking for abnormalities to make the structural diagnosis and define it. Results: Of the 108 patients included in the study, 51 patients (Group A) were refractory to medical treatment and 57 patients (Group B) showed an improvement with medical treatment. We quantified the frequency of structural lesions confirmed by neuroimaging in both groups. The results showed a statistically significant difference of 84.31% of patients in Group A with a confirmed structural lesion in an MRI study versus 52.63% of patients in Group B (p = 0.004 [odds ratio = 4.85,). Conclusion: Our results support the association between structural lesions diagnosed with MRI and drug-resistant epilepsy. Thus, this finding gives a chance of an opportune and precise approach for the surgical treatment of these patients.