Background: Audio-analgesia, the ability of music to reduce the perception of pain, has been a significant field of research in the past decade. This study aimed to investigate the impact of the musical constructs of harmonicity and rhythmicity on acute, post-operative pain. Method: 98 patients scheduled for primary total knee arthroplasty were randomly allocated at their pre-admissions clinic to one of four music listening groups, receiving commercially-available music. The participants in the experimental groupings were randomised according to the musical constructs of high/low harmonicity and rhythmicity (four possible groups; + +, + –, – +, – –). Music groups were compared against a silent control group, receiving quiet relaxation (with headphones). After surgery using a standardised anaesthetic regiment, all participants undertook a 15-minute listening/ silent intervention on the ward for each day of their in-patient stay (max. 5 days). The primary endpoint was pain intensity. Salivary cortisol concentrations and mood stability were also monitored. Qualitative data was collected via daily feedback and assessed through thematic category analysis. Results: A significant reduction in pain intensity from pre- to post-test was shown for all participants (p < 0:0005), but with no difference between groups (F(4;68) = 1:331, NS). Quiet relaxation (mean change: 22.27%) was as effective as music listening (mean change: 37.47%). Salivary cortisol concentrations showed an interaction between music with high harmonicity and high rhythmicity (+ +) and music of low harmonicity and rhythmicity (– –). + + music reduced cortisol concentration to a greater extent on Day 1 (p < :05) than – – music. There was no significant difference between groups in mood disturbance. Qualitative data revealed four thematic categories of response: psychological, physiological, musicological and methodological, overall indicating that patients utilised their intervention as a distracting and relaxing cognitivecoping strategy. Conclusion: Music is a viable therapeutic medium which reduced pain, as effectively as quiet relaxation. Compositional constructs were minimally active in the degree of analgesia and physiological changes experienced by patients, but where this did occur, it could be related to Berlyne’s inverted-U model of musical preference (Berlyne, 1971). The positive reception of the interventions and the associated benefits, supports the inclusion of cognitive-coping strategies in multi-modal care pathways.