Emollient cream moisturizers are often used on premature newborns in neonatal intensive care units without accurate knowledge of the risks or benefits to the neonate. We prospectively compared premature neonates treated with a water-in-oil emollient cream for up to 16 days to untreated premature neonates. The study was completed in a neonatal intensive care unit on neonates admitted for respiratory distress and/or possible sepsis. Thirty-four neonates, between 29 and 36 weeks estimated gestational age, entered the study. One-half of the neonates were treated twice a day with an water-in-oil emollient cream, and the other half served as controls. The skin condition of the neonates' hands, feet, and abdomen was evaluated on entering the study and twice a week. Fungal cultures and quantitative bacterial cultures were obtained from the axilla and abdomen on entering the study and twice a week. The mean gestational age of the treated neonates was 32.3 weeks, whereas the mean gestational age of the control neonates was 32.5 weeks. The neonates treated with emollient cream demonstrated statistically less dermatitis of their hands (day 2 through day 11), their feet (day 2 through day 16), and their abdomen (day 7 through day 11). Fungal cultures and quantitative bacterial cultures of the abdomen and axilla were equivalent in both groups. These studies document that emollient cream moisturizer therapy of premature neonates decreases dermatitis without changing the microbiological flora.