High stress may diminish a surgeon’s performance in the operating theatre (OT) and lead to a chronic stress phenomenon. Music is perceived to reduce stress in the OT, however the psycho-physiological effects of music on intra-operative stress in inexperienced and experienced operators is incompletely understood. The effect of music on the psychological (Six-Item State-Trait Anxiety Inventory [STAI-6] and Surgical Taskload Index [SURG-TLX]) and physiological (cardiorespiratory, cerebral perfusion, electrodermal activity) responses was determined to a simulated surgical task (carotid patch-angioplasty) in 15 medical students (MS) and 12 vascular surgeons (VS) under stressing conditions in a randomised crossover design. Comparative analysis was performed by paired two-tailed t-tests and ANOVA. The VS group made fewer errors, were quicker and rated their skill higher, though there was no effect of music on performance. There was a main effect on SURG-TLX scores with an increase of 30.2 (20.2-40.1) from baseline and STAI-6 scores 3.0 (1.7-4.3). HR, MCA Vm, RR, PETCO2 and SNS index were increased, while EDA and PNS index decreased during the task, indicative of a physiological stress response, though listening to music did not attenuate these responses. There was a modest change in composite measures of heart rate variability (HRV) indicating higher sympathetic activity in the presence of music, however there was no difference in psychological or other physiological measure. Future research directions would be to explore the clinical significance of the HRV difference or consider alternative research methodology.