IMPORTANCE Emerging evidence suggests that the use of moisturizers on newborns and infants (ie, from birth to 6 months of age) is potentially helpful in preventing the development of atopic dermatitis. OBJECTIVE To investigate the cost-effectiveness of using a daily moisturizer as prevention against atopic dermatitis among high-risk newborns. DESIGN, SETTING, AND PARTICIPANTS In a cost-effectiveness analysis, the average cost of total-body moisturization using 7 common moisturizers from birth to 6 months of age was determined for male and female infants.We assumed the same unit of weight per moisturizer used for a given body surface area. Based on previously reported data (relative risk reduction of 50%), the incremental gain in quality-adjusted life-years (QALYs) was determined using a 6-month time window. The cost-effectiveness of each moisturizer was determined by assuming equal efficacy. A sensitivity analysis was conducted by varying the relative risk from 0.28 to 0.90. INTERVENTIONS Use of prophylactic moisturizing compounds. MAIN OUTCOMES AND MEASURES The primary outcomeswere the incremental cost-effectiveness values ($/QALY) for each moisturizer in preventing atopic dermatitis during a 6-month time window. RESULTS The calculated amount of daily all-body moisturizer needed at birth was 3.6 g (0.12 oz) per application, which increased to 6.6 g (0.22 oz) at 6 months of age. Of the 7 products evaluated, the average price was $1.07/oz (range, $0.13/oz-$2.96/oz). For a 6-month time window, the average incremental QALY benefit was 0.021. The sensitivity analysis showed that the incremental gain of QALY ranged from 0.0041 to 0.030. Petrolatum was the most cost-effective ($353/QALY [95%CI, $244-$1769/QALY) moisturizer in the cohort. Even assuming the lowest incremental QALYs for the most expensive moisturizer, the intervention was still less than $45 000/QALY. CONCLUSIONS AND RELEVANCE Overall, atopic dermatitis represents a major health expenditure and has been associated with multiple comorbidities. Daily moisturization may represent a cost-effective, preventative strategy to reduce the burden of atopic dermatitis.