The influence of environmental factors on atopic dermatitis (AD) has been investigated in many cross-sectional studies. It remains however unclear if they could influence AD development early in life. This prospective birth cohort study aimed to monitor aspects of family lifestyle and child's nutrition within a Caucasian population and to assess its association with AD development over the first 2 years of life. Genetic predisposition was evaluated based on family history and profilaggrin genotyping. Of 149 included children, 36 developed AD. Infants with a family history of atopy developed AD 2.6 times more frequently (30 of 97) than infants without atopic predisposition (6 of 52). Genotyping was carried out on 50% of the children included. Profilaggrin mutations (R501X, 2282del4, R2447X, and S3247X) were infrequent in our population. Lower incidence of AD was observed in infants exposed to a damp housing environment, lower household income, and smoking mothers with a higher but not with a lower education level.Conclusion: Family history of atopy was a significant risk factor for AD regardless of the most common, currently defined, FLG mutations. Humidity at home and passive smoking seem associated with AD development in infancy. What is Known: • Atopic dermatitis (AD) is associated with mutations in various genes of the immune system and the epidermal barrier complex in particular filaggrin (FLG) mutation. • Inherited factors alone cannot explain the rising AD; environmental factors are therefore likely to play a decisive role in this rise but the exact role that these factors may play in increasing AD risk in infancy remains unclear. Moreover, the relationship between environmental factors and AD has been the focus of mostly cross-sectional studies and not prospective studies. What is New: • This prospective birth cohort study demonstrates that family history of atopy is a significant risk factor for AD regardless of the most common, currently defined, FLG mutations. • A lower incidence of AD was observed in infants exposed to a moist housing environment, lower household income, and smoking of mothers with a higher but not with a lower education level.