Background In Japan, eHealth for infants and mothers is currently an important aspect, but its effectiveness has rarely been examined. For infants, skin problems, including atopic dermatitis (AD), which is known to lead to other allergic diseases, are one of the most common conditions. Mothers of infants are prone to experiencing parenting stress, which adversely affects mothers’ and children’s well-being. Additionally, studies have reported that AD among offspring enhances parenting stress, and postnatal maternal psychological problems can increase the risk of AD in children. Objective This study evaluated the effectiveness of pediatric teleconsultation for preventing AD in infants and reducing parenting stress in mothers in Japan. Methods The study was an open-label, randomized, parallel-armed controlled trial. In total, 318 pairs of infants and mothers in the Yokohama City Sakae Ward were recruited when they submitted birth cards to the ward, received the explanation about the trial, and provided informed consent on the website for this trial. Eligible pairs of infants and mothers were randomly assigned to the intervention group (n=140) or the control group (n=138). Participants in the intervention and control groups received routine postnatal care from local government services. In addition, participants in the intervention group had the option to combine routine pediatric services with teleconsultation and email newsletters without charge from the date of registration until the infant turned 4 months. Primary outcomes were (1) the prevalence of AD in infants diagnosed based on the United Kingdom Working Party criteria and (2) parenting stress and mental status of mothers assessed using the Parenting Stress Index-Short Form (PSI-SF) and General Health Questionnaire-12 (GHQ-12). Data were collected by the ward office staff and researcher during the 4-month checkup. Results The prevalence of AD in infants was significantly lower in the intervention group than in the control group during the 4-month checkup (20% vs 33%, P=.02; relative risk ratio, 0.709 [95% CI 0.519-0.969]). No significant differences were observed in the PSI-SF and GHQ-12 scores between the 2 groups. There was a significant difference in the prevalence of AD between participants who used teleconsultation services and email newsletters, participants who did not use teleconsultation services but received email newsletters, and participants who neither received nor used either service (18% vs 22% vs 33%, P=.048). Conclusions This is the first randomized controlled trial demonstrating that routine pediatric care combined with teleconsultation and email newsletters was effective in reducing the prevalence of AD in infants. The findings highlight the potential of pediatric eHealth to become a useful new strategy for preventing AD. Trial Registration University Hospital Medical Information Network Clinical Trials Registry UMIN000029774; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034022