Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection.Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100β, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared.Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg–1 h–1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min–1 m–2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05).Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol.Clinical trial registration. NCT02113358.