Abstract: BACKGROUND: Infants with in-utero exposure to opioids are at risk Neonatal Opioid Withdrawal Syndrome (NOWS) and non-pharmacological methods of care, like swaddling, quiet ambient environment are routinely recommended but are not systematically studied. We hypothesized that opioid exposed infants can tolerate whole body massage while hospitalized. METHODS: This is a prospective observational study (August 2017 to January 2019) and infants of mothers having a history of opioids use (OUD) were included. Infants received whole body massage for 30 minutes from birth till discharge home. Infants heart rate (HR), respiratory rate (RR), systolic (sBP) and diastolic blood pressure (dBP) were recorded prior to and at the end of massage session. RESULTS: The pilot study enrolled 30 infants. The mean birth weight and gestational age were 38±1 weeks and 2868±523 grams, respectively. All massage sessions were well tolerated. There was marked decrease in HR, systolic and diastolic BP and RR, (p < 0.01) in all study infants post massage, more profound among infants with NOWS (p < 0.01) than without NOWS. CONCLUSIONS: Whole body massage is very well tolerated by infants with in-utero opioid exposure. Infants with NOWS had marked decrease in their HR and BP from their baseline after massage.