Purpose <p>This randomised controlled trial investigated the effect of Surgical Pleth Index (SPI) guided sufentanil administration on intraoperative sufentanil consumption compared to routine care in patients with a combination of general anaesthesia and regional anaesthesia having trauma and orthopaedic surgery.</p> Methods <p>Eighty patients with a combination of general anaesthesia and regional anaesthesia undergoing trauma or orthopaedic surgery were randomised into two groups to receive either sufentanil guided by SPI monitoring or by routine care (Control). The primary endpoint was intraoperative sufentanil consumption. Secondary endpoints were postoperative pain level, opioid consumption, incidence of nausea, duration of time in the post-anaesthesia care unit (PACU) and quality of recovery.</p> Results <p>The median intraoperative sufentanil administration adjusted to bodyweight and surgery duration did not differ between the groups: SPI guided group 2.29 (interquartile range, IQR 0.29 to 6.91), Control 1.65 (IQR 0.83 to 2.63) µg·kg⁻¹·min⁻¹*1000 (<i>P</i> = 0.906). The relative risk for receiving intraoperative sufentanil was RR 0.909 (95% CI 0.723 to  1.143, <i>P</i> = 0.414). Median morphine equivalents administered in the 24&#xa0;h after discharge from the PACU were 3.8 (IQR 0.0 to 22.5) in the SPI guided group and 19.1 (IQR 3.8 to 30.0) mg (<i>P</i> = 0.021) in the control group without adjustment for multiple testing. Other secondary endpoints showed no differences. </p> Conclusion <p>SPI guided sufentanil administration did not reduce intraoperative sufentanil consumption compared to routine care in patients having trauma and orthopaedic surgery with a combination of general anaesthesia and regional anaesthesia.</p> Trial registration <p>Clinicaltrials.gov identifier NCT06040307 (registered September 8, 2023).</p>