We investigated the effect of house dust mite (HDM)-allergen avoidance on the development of respiratory symptoms, atopic dermatitis, and atopic sensitization by performing a double blind, placebo-controlled trial. In total, 1,282 allergic pregnant women were selected (416 received HDM allergen-impermeable mattress covers for the parents' and child's mattress in the third trimester of pregnancy [active], 394 received placebo covers, 472 received no intervention). Data on allergen exposure, clinical symptoms, and immunoglobulin E were collected prospectively. The prevalence of night cough without a cold in the second year of life was lower in the group with active covers compared with the group with placebo covers (adjusted odds ratio 0.65; 95% confidence interval 0.4-1.0). No effect of the intervention was seen on other respiratory symptoms, atopic dermatitis, and total and specific immunoglobulin E. It can be concluded that application of HDM-impermeable mattress covers on the child's and parents' beds reduced night cough, but not other respiratory symptoms, atopic dermatitis, and atopic sensitization in the first 2 years of life. Follow-up will determine the long-term effect of the intervention on the development of atopic disease.