The aim of this study was to evaluate the effect of house dust mite impermeable covers on asthma-specific health-related quality of life in adult asthmatic patients that were trained in guided self-management. In a 2-year randomized placebo-controlled clinical trial, information on the quality of life was collected. The improvement of Mini Asthma Quality of Life Questionnaire (AQLQ) score in the allergens-avoidance group (0.26) was comparable to the improvement in the placebo group (0.30) and not significant. HDM-impermeable covers for pillows, duvets, and mattresses did not result in improved health-related quality of life.