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Background Postoperative delirium is a frequent complication with negative consequences for neurosurgical patients. Recorded music has been shown to reduce the incidence of delirium, however its economic benefit remains unclear. This study aimed to investigate the cost-effectiveness of perioperative music in preventing postoperative delirium. Methods This study used data from a randomized controlled trial (Clinical Trials.gov; NCT04649450) that compared the effect of perioperative music with standard of clinical care on the occurrence of postoperative delirium in patients undergoing craniotomy at the Erasmus Medical Centre. The primary outcome of this study is the cost-effectiveness of the music intervention. A trial-based cost-effectiveness analysis (CEA) was conducted from a societal perspective. Mean costs were calculated using bootstrapping with 95% confidence intervals. Secondary outcomes included postoperative complications, mortality, cognitive functioning, and quality of life. Costs and patient outcomes were assessed separately for the initial hospital admission and long-term follow-up until 6 months after discharge. Results This study included 91 patients in the intervention group and 93 in the control group. On average, medical costs during initial admission were lower, albeit not statistically significant, in the music group compared to the control group (€ 11,819 vs. € 13,106), mostly due to a shorter length of stay. Total costs over the 6-month period were nearly identical between the groups, at € 18,587 and € 18,571 in the music and control group, respectively. Conclusions Pre-recorded perioperative music may be a cost-effective intervention for reducing postoperative delirium in neurosurgical patients, possibly by decreasing healthcare utilization and costs during primary admission. Further studies are needed to confirm its potential as a cost-effective intervention.