BACKGROUND: Atopic parents may adopt lifestyle characteristics that allegedly protect against atopic disease. If this is true, infants from atopic parents will be characterized by low-risk behaviour. Consequently, aetiologic studies on lifestyle factors and allergic disease in childhood may be biased by confounding by indication. OBJECTIVE: We explored whether the prevalence of 'prudent' lifestyle characteristics differs between atopic and non-atopic families. METHODS: Information about a family history of atopic manifestations and lifestyle characteristics was collected by repeated questionnaires in the Dutch KOALA Birth Cohort Study in 2469 infants from families with divergent lifestyle practices (conventional vs. alternative). RESULTS: In conventional lifestyle families, infants were less often exposed to environmental tobacco smoke when parents were atopic than when they were non-atopic (10.0% vs. 14.7%, P=0.001). In alternative lifestyle families, exposure to smoking was very rare in both groups (1.7% vs. 2.6%). Pets were less often present in families with than without parental atopy (38.8% vs. 51.1%, P=0.008 for conventional lifestyle families; 43.0% vs. 48.4%, P=0.014 for alternative lifestyle families). Infants with atopic siblings had less often been vaccinated according to the standard scheme than infants with non-atopic siblings in conventional lifestyle families (76.6% vs. 85.5%, P<0.001). In alternative lifestyle families, the difference was in the same direction but not statistically significant (30.1% vs. 40.5%, P=0.143). Antibiotic use, breastfeeding and consumption of organic foods were unrelated to a family history of atopic manifestations. CONCLUSION: Some 'prudent' lifestyle characteristics differed between atopic and non-atopic families, depending on whether atopic manifestations were present in parents or older siblings. This has important consequences for the validity in epidemiological studies on the aetiology of allergy in children. Confounding by indication because of a family history of atopic manifestations can best be controlled for by considering atopy in parents and siblings as separate confounders.