Background: Music-based intervention has been advocated as a nonpharmacologic approach for the perioperative control of pain and anxiety in surgical patients. However, its impact on patients with preoperative anxiety has not been clearly established. Our study aimed to examine the impact of music-based intervention administered before, during, and after surgery on postoperative opioid consumption and pain levels, as well as preoperative anxiety, depression, and pain catastrophizing. We hypothesized that, compared to a control group, music-based intervention would be effective in reducing opioid requirements and mood disorders. Methods: This study was a single-center, prospective, single-blinded, randomized controlled trial. Inclusion criteria isame-day or observation surgery. Exclusion criteria included American Society of Anesthesiologists physical status IV, use of spinal anesthesia, PROMIS Anxiety T-scores ≤ 57.4 and ≥74.1, preoperative chronic opioid use, transgender surgery, and history of drug or alcohol abuse. Music-based intervention was developed by a certified music therapist. Each patient was randomized to receive standard of care (SC) or SC plus music-based intervention before, during, and after surgery. The primary end point was postoperative oral morphine equivalents (OMEs) over 5 days following surgery using the area under the curve (AUC)Secondary end points were PROMIS Anxiety, PROMIS Depression scores Pain Catastrophizing Scale scores, postoperative nausea and vomiting, time of hospital discharge, and patient satisfaction (0 = totally unsatisfied to 10 = completely satisfied). Results: A total of 75 patients were randomized to a music-based intervention (n = 33) or control (n = 42) group. Patients in the music-based intervention group consumed 56.7% less opioids than those in the control group (AUC was 2.8 in the music-based intervention group vs. 6.4 in the control group, absolute standardized mean difference (aSMD) = 0.34 (-0.17, 0.85)). No difference in pain scores was recorded between groups. Music-based intervention also reduced anxiety on postoperative day (POD)2 (aSMD = 0.38 (-0.16, 0.91)), depression on POD2 (aSMD = 0.31 (-0.23, 0.84)) and POD4 (aSMD = 0.24 (-0.29, 0.77)), and pain catastrophizing on POD1 (aSMD = 0.24 (-0.3, 0.77)). Conclusions: Our data support the use of music-based intervention to reduce postoperative opioid requirements. Music-based intervention may also reduce anxiety, depression, and pain catastrophizing.