Objective To observe the effect of remimazolam on postoperative delirium (POD) in patients undergoing endovascular neurosurgery. Methods Patients who were scheduled for endovascular neurosurgery under general anesthesia in Xijing Hospital, Air Force Medical University from July 2021 to June 2022 were selected. According to the block randomization method, they were divided into two groups: group propofol (group P) and group remimazolam (group R). Patients in group P were intravenously injected with 1.0‒1.5 mg/kg of propofol for anesthesia induction, followed by intravenous infusion of propofol at 4‒10 mg·kg−1·h−1 for maintenance. Meanwhile, patients in group R were intravenously injected with 0.1 mg/kg of remimazolam for anesthesia induction, followed by intravenous infusion of remimazolam at 0.3‒0.7 mg·kg−1·h−1 for maintenance. Then, both groups were compared for general information, preoperative comorbidities, the duration of operation, and intraoperative use of vasoactive agents. Venous blood samples were collected 20 min before surgery and 5 min after surgery. The levels of serum interleukin (IL)‑6, S100 calcium binding protein β (S100β) and tumor necrosis factor‑α (TNF‑α) were detected by double antibody sandwich ABC‑enzyme‑linked immunosorbent assay (ELISA) method. Furthermore, the Confusion Assessment Method‑intensive care unit (CAM‑ICU) was used to evaluate delirium 30 min after extubation, and at postoperative 1 d and 3 d. Results A total of 129 patients completed the study, including 64 patients in group P and 65 patients in group R. There was no statistical difference in general information, preoperative comorbidities and the duration of operation between the two groups (P>0.05). There was no statistical difference in the incidence of POD between two groups 30 min after extubation, and at postoperative 1 d and 3 d (P>0.05). There was no statistical difference in the levels of serum IL‑6, TNF‑α and S100β between two groups before and after surgery (P>0.05). Compared with those before surgery, there was no statistical difference in IL‑6,TNF‑α and S100β levels between the two groups after surgery (P>0.05). Group R presented a lower rate of vasopressor use than group P (P<0.05), and no statistical difference was found in the rate of antihypertensive agent and atropine use between the two groups (P>0.05). Conclusions Compared with propofol, remimazolam for general anesthesia does not increase the incidence of POD after endovascular neurosurgery, without significant changes in the levels of serum IL‑6, TNF‑α and S100β.