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Background Surgery in the beach chair position (BCP) may reduce cerebral blood flow and oxygenation, resulting in neurological injuries. The authors tested the hypothesis that a ventilation strategy designed to achieve end-tidal carbon dioxide (ECO2′) values of 40–42 mm Hg would increase cerebral oxygenation (SctO2) during BCP shoulder surgery compared with a ventilation strategy designed to achieve ECO2′ values of 30–32 mm Hg. Methods Seventy patients undergoing shoulder surgery in the BCP with general anaesthesia were enrolled in this randomized controlled trial. Mechanical ventilation was adjusted to maintain an ECO2′ of 30–32 mm Hg in the control group and an ECO2′ of 40–42 mm Hg in the study group. Cerebral oxygenation was monitored continuously in the operating theatre using near-infrared spectroscopy. Baseline haemodynamics and SctO2 were obtained before induction of anaesthesia, and these values were then measured and recorded continuously from induction of anaesthesia until tracheal extubation. The number of cerebral desaturation events (CDEs) (defined as a ≥20% reduction in SctO2 from baseline values) was recorded. Results No significant differences between the groups were observed in haemodynamic variables or phenylephrine interventions during the surgical procedure. SctO2 values were significantly higher in the study 40–42 group throughout the intraoperative period (P<0.01). In addition, the incidence of CDEs was lower in the study 40–42 group (8.8%) compared with the control 30–32 group (55.6%, P<0.0001). Conclusions Cerebral oxygenation is significantly improved during BCP surgery when ventilation is adjusted to maintain ECO2′ at 40–42 mm Hg compared with 30–32 mm Hg. Clinical trial registration ClinicalTrials.gov NCT01546636. [ABSTRACT FROM AUTHOR]