Objective To investigate the safety of etomidate speech and memory-Wada test (eSAM-Wada) and the efficacy of eSAM-Wada in the function assessment of motor, speech and memory. Methods The clinical data of five patients with intractable epilepsy who underwent eSAM-Wada in the Department of Neurosurgery, Shenzhen University General Hospital were retrospectively analyzed. During the procedures of digital subtraction angiography (DSA), 2 mg etomidate was administered intravenously after the microcatheter reached the target vessel, followed by 0.004 mg·kg^-1·min^-1 continuous intravenous pumping. The changes of motor, speech and memory functions and intraoperative adverse effects were observed. Results All the five patients completed the whole procedure of eSAM-Wada, and two patients completed eSAM-Wada under vascluar superselection. Of the five patients, three were left-handed and two were right-handed. Among the three left-handed patients, the speech dominant hemisphere was located in the left hemisphere in two patients, while the other two right-handed patients had their speech dominance in the left hemisphere. Four patients had extensive lesions in the left hemisphere. The dominant side of memory was located in the left temporal lobe in two cases, bilateral dominance in one case, and completely transfering to the right temporal lobe in one case. Two patients underwent subsequent resection and one patient underwent stereotactic electroencephalogram (SEEG)-guided thermocoagulation. One patient had transient postsurgical paralysis over the left extremities. The changes of motor, speech and memory functions for these patients were consistent with the results of eSAM-Wada. Two patients had seizures, which might be related to the rapid intravenous administration of etomidate in the procedure. After prolonging the administration time to >30 s, the remained two patients had no seizures. Conclusion eSAMWada is a reliable and relatively safe method for comprehensive evaluation of motor, speech and memory functions in epilepsy surgery. Combined with vascular superselective technology, it can provide more effective guidance for craniocerebral surgery involving functional areas.