Patients in intensive care units (ICUs) often experience stress and anxiety. Although stress and anxiety can be pharmacologically attenuated, some drugs cause adverse side effects such as bradycardia, immobility, and delirium. There is thus a need for an alternative treatment with no substantial adverse effects. Music intervention is a potential alternative. In the present study, we used cortisol levels, subjective questionnaires, and physiological parameters to explore the anxiety-reducing effects of music intervention in a sample of ICU patients on mechanical ventilation. Patients admitted to the ICU for ≥ 24 hr were randomly assigned to the music intervention (n = 41) or control group (n = 44). Music group patients individually listened to music from 4:00 to 4:30 p.m.; control group patients wore headphones but heard no music for the same 30 min. Anxiety was measured using serum cortisol levels, the Chinese Version of the State-Trait Anxiety Inventory, the Visual Analogue Scale for Anxiety, heart rate, and blood pressure. After adjusting for demographics, analysis of covariance showed that the music group had significantly better scores for all posttest measures (p < .02) and pre–post differences (p < .03) except for diastolic blood pressure. Because of music intervention’s low cost and easy administration, clinical nurses may want to use music to reduce stress and anxiety for ICU patients. A single 30-min session might work immediately without any adverse effects. However, the duration of the effect is unclear; thus, each patient’s mood should be monitored after the music intervention.