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Premature infants are exposed to high levels of noise in the neonatal intensive care unit (NICU).This study evaluated the effect of a relaxing music therapy intervention composed by artificial intelligence on respiratory rate, systolic and diastolic blood pressure, and heart rate.A double-blind, randomized, controlled trial was conducted in the NICUs of 2 general public hospitals in Andalusia, Spain. Participants were 17 healthy premature infants, randomly allocated to the intervention group or the control group (silence) at a 1:1 ratio. To be included in the study, the subjects were to be 32 to 36 weeks of gestation at birth (M= 32.33; SD = 1.79) and passed a hearing screening test satisfactorily. The intervention lasted 20 minutes, 3 times a day for 3 consecutive days, while infants were in the incubator. Infants' heart rate, respiratory rate, and blood pressure were assessed before and after each intervention session.After each session, the respiratory rate decreased in the experimental group (main between-groups effect (F1,13 = 6.73, P = .022, η2partial = 0.34). Across the sessions, the heart rate increased in the control group (main between-groups effect, F1,11 = 5.09, P = .045, η2partial = 0.32).Future studies can use this music intervention to assess its potential effects in premature infants.Nurses can apply the relaxing music intervention presented in this study to ameliorate the impact of the stressful environment on premature infants.