Background Awake craniotomy with intraoperative brain mapping in the surgical management of brain lesions at eloquent areas has been reported to be associated with better neurological outcome and more extensive resection. Conscious sedation avoids the risks of general anesthesia, reduces the rate of ICU admissions, and shortens the length of hospital stay. Aim of the study The aim of the is to compare the efficacy and safety of dexmedetomidine with midazolam during procedural sedation of awake craniotomy patients. Patients and methods A quasi-experiment conducted upon 24 awake craniotomy patients. Patients were of American Society of Anesthesiologists I/II, of both sexes, 21–65 years. Scalp block was done. The patients were divided into two groups: group D is the dexmedetomidine group (n=12) and group M is the midazolam group (n=12). Group D: 1 μg/kg dexmedetomidine was administered intravenously over 20 min, followed by continuous infusion of 0.1–0.7 μg/kg/h. Fifteen minutes before starting cortical mapping, the dose of dexmedetomidine was reduced to 0.1 μg/kg/h. Group M: midazolam was administered as an intravenous loading dose of 0.1 mg/kg given slowly over 10 min followed by infusion of 0.03–0.2 mg/kg/h. Fifteen minutes before starting cortical mapping, the dose of midazolam was reduced to 0.03 mg/kg/h. Results Success rate was significantly higher in group M compared with group D (100 vs. 91.7%). Duration of postoperative recovery from sedation was statistically significantly longer in group M compared with group D (24±1 vs. 18±8). Three (25%) cases in group D experienced intraoperative seizures and one (8.3%) case could not be controlled and awake technique was aborted. Patients had memories of the procedure (66.7% in group D to 16.7% in group M) with statistically significant difference. Conclusion Both dexmedetomidine and midazolam were safe and efficient during awake craniotomy. Midazolam had a higher success rate, lower incidence of intraoperative seizures, and higher incidence of amnesia. Dexmedetomidine had more rapid recovery. Keywords: awake craniotomy, dexmedetomidine, midazolam