Aims:The aim of the study was to compare the effect of mannitol (M) and hypertonic saline (HTS) on brain relaxation and electrolyte balance.Settings and Design:Prospective, randomized, double-blind study.Subjects and Methods:A total of 114 patients with American Society of Anesthesiologists status II and III, scheduled to undergo craniotomy for supratentorial brain tumor resection were enrolled. Patients received 5 ml/kg 20% mannitol (n = 56) or 3% HTS (n = 58) at the start of scalp incision. Hemodynamics, fluid balance and electrolytes, were measured at 0, 15, 30, and 60 min and 6 h after infusion. Intensive Care Unit (ICU) stay between the two groups was also recorded. The surgeon assessed brain relaxation on a four-point scale (1 = Relaxed, 2 = Satisfactory, 3 = Firm, 4 = Bulging). Appropriate statistical tests were used for comparison; P < 0.05 was considered significant.Results:Brain relaxation conditions in the HTS group (relaxed/satisfactory/firm/bulging, n = 28/20/5/3) were better than those observed in the M group (relaxed/satisfactory/firm/bulging, n = 17/21/11/9). The levels of serum sodium were higher in the HTS group (P < 0.001). The average urine output was higher in the M group (5.50 ± 0.75 L) than in the HTS group (4.38 ± 0.72 L) (P < 0.005). There was no significant difference in fluid input, ICU stay, and hospital days between the two groups.Conclusion:We concluded that HTS provided better brain relaxation than mannitol during elective supratentorial brain tumor surgery, without affecting ICU and hospital stay.