AbstractBackgroundThe effectiveness of moisturizers in preventing infant atopic dermatitis (AD) remains unclear. We previously showed that using 2e moisturizer of commercial moisturizer (Shiseido Japan Co., Ltd.) at least once a day significantly prevented AD in infants as compared with as‐needed petroleum jelly. This trial aimed to determine the effectiveness of twice‐ or once‐daily application of Fam's Baby moisturizer (Fam's Inc.) in preventing AD compared with once‐daily 2e moisturizer.MethodsThis trial was a single‐centre, three‐parallel‐group, assessor‐blinded, superiority, individually randomized, controlled, phase II trial that was conducted from 25 August 2020 to 28 September 2021. We randomly assigned 60 newborns with at least one parent or sibling who has AD to receive Fam's Baby moisturizer twice daily (Group A) or once daily (Group B), or 2e once daily (Group C) in a 1:1:1 ratio until they were 32 weeks old. The primary outcome was the time of AD onset.ResultsAtopic dermatitis was observed in 11/20 (55%), 5/20 (25%) and 10/20 (50%), infants in Groups A, B and C, respectively. Cumulative incidence values for AD according to the Kaplan–Meier method showed that infants in Group B tended to maintain an intact skin for a longer period than those in Group C (median time, not reached [NR] vs. 212 days, log‐rank test, p = 0.064). Cox regression analysis showed that the risk of AD tended to be lower in Group B (hazard ratio with group C as control, 0.36; 95% confidential intervals: 0.12–1.06). No serious adverse events occurred in any of the enrolled infants.ConclusionFam's Baby moisturizer may better prevent AD than 2e. Further large‐scale trials should be performed to confirm the efficacy of Fam's Baby moisturizer in preventing AD in infants.