OBJECTIVE: Standard resective treatment of mesial temporal lobe epilepsy (MTLE) includes anteromesial temporal resection or amygdalohippocampectomy. One potential risk of these surgeries, especially in patients with MRI-negative findings, is postoperative memory impairment. An alternative to resective procedures that aim to preserve the neuropsychological profile are multiple hippocampal transections (MHT). The objective of transections is to interrupt the longitudinal pathways of the hippocampus to prevent the spread of epileptic seizures while preserving the memory circuits. Previously performed MHT procedures were guided by questionable intraoperative electrocorticography. At our institution, we have developed and tested a modified technique to achieve complete multiple hippocampal transections. METHODS: Patients with pharmacoresistant unilaterally lateralized MTLE and MRI-negative findings with high risk of neuropsychological deterioration were indicated for complete MHT. Comprehensive neuropsychological and epileptological evaluations and MRI follow-ups were conducted one year and two years postoperatively. The primary evaluated parameters were seizure reduction and significant changes in neuropsychological performance (+/- 1 SD). RESULTS: Complete MHTs were performed on three patients who completed two-year follow-up. Two MHTs were performed on the right and one on the left side. Two patients are classified as Engel 1 and one patient as Engel 3. Two years after surgery neuropsychological evaluation did not show significant decrease in memory performance and performance in majority of cognitive tests. One-year MRI follow-up showed decrease of volume of hippocampus in all three patients. CONCLUSION: This modified technique of MHT in patients with MTLE and MRI-negative findings led to seizure reduction while preserving their neuropsychological performance.