Background: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 2 doses of 3% HS during elective supratentorial brain tumour surgery.Methods: 60 patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 3 mL/kg (group L) or 5 mL/kg (group H) of 3% HS administered at skin incision. Brain relaxation was assessed after dura opening on a scale ranging 1–4 (1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain, 4 = bulging brain). Hemodynamic variables and laboratory values (blood gases, osmolarity, haematocrit, and lactate) were collected before HS infusion and 30, 120 and 360 min after it. Presence of midline shift, postoperative complications, PCU and hospital stay, and mortality after 30 days were also recorded.Results: There was no difference in brain relaxation, with 2.0 (1.0–3.0) and 2.0 (1.0–2.3) (P = 0.535) for patients in groups L and H, respectively. If adjusted for the presence of midline shift, 50% of patients had adequate brain relaxation scores (grades 1 and 2) in group L and 61% in group H (OR 0.64, CI = 0.16-2.49, P = 0.515). No significant differences in perioperative outcome, mortality and length of PCU and hospital stay were observed.Conclusion: 3 mL/kg of 3% HS result in similar brain relaxation scores as 5 mL/kg in patients undergoing craniotomy for supratentorial brain tumour. This study reveals that both high and low doses of 3% HS may be less effective on intraoperative brain relaxation in patients with midline shift.