Several studies have demonstrated that early intervention may modulate the natural course of atopic disease. The objective of this study was to prevent sensitization to house dust mite and food allergens, as well as development of atopic symptoms, during infancy. To achieve this we employed the combination of an educational package with the use of mite allergen-impermeable mattress encasings. A multi-center European, population-based, randomized controlled study of children at increased atopic risk [study on the prevention of Allergy in Children in Europe (SPACE)] was performed in five countries (Austria, Germany, Greece, Great Britain, Lithuania) and included three cohorts of schoolchildren, toddlers and newborns. We report on the newborn cohort. A total of 696 newborns were included in Austria, Great Britain and Germany. Inclusion criteria were a positive history of parental allergy and a positive skin-prick test or specific immunoglobulin E (IgE) of ≥ 1.43 kU/l against at least one out of a panel of common aeroallergens in one or both parents. At 1 year of age the overall sensitization rate against the tested allergens [dust mite allergens: Dermatophagoides pteronyssinus and D. farinae (Der p and Der f, respectively)] and food allergens (egg, milk) in the prophylactic group was 6.21% vs. 10.67% in the control group. The prevalence of sensitization against Der p was 1.86% in the prophylactic group vs. 5% in the control group. In conclusion, we demonstrated, in a group of newborns at risk for atopic diseases, that the sensitization rate to a panel of aero- and food allergens could be effectively decreased through the use of impermeable mattress encasings and the implementation of preventive measures that were easy to perform.