As asthma is the most common chronic disease in childhood, much attention is directed towards primary prevention. Here, the clinical effectiveness of a multifaceted educational prevention was studied. A total of 476 high-risk children were recruited during the prenatal period by general practitioners and randomised to either: 1) a control group, receiving usual care; or 2) an intervention group in which families received instruction from nurses on how to reduce exposure of newborns to mite, pet and food allergens, and passive smoking. A total of 443 infants were followed-up for 2 yrs. At 2 yrs of age, the intervention group (n = 222) had less asthma-like symptoms, including wheezing, shortness of breath and night-time cough, than the control group (n = 221). No significant differences in total and specific immunoglobulin E were found between the groups. During the first 2 yrs of life, the incidence of asthma-like symptoms was similar in both groups; however, subanalysis revealed a significant reduction in the female, but not in the male, intervention group. In conclusion, the intervention used in this study was not effective in reducing asthma-like symptoms in high-risk children during the first 2 yrs of life, although it was modestly effective at 2 yrs. Follow-up is necessary to confirm whether the intervention can actually prevent the development of asthma.