The present multicentre study was aimed at comparably assessing the benefits and burdens associated with home mechanical ventilation (HMV). Hospitalisation, side-effects and health-related quality of life (HRQL) were assessed 1 month and 1 yr following HMV establishment using the Medical Outcome Study 36-Item Short-form Health Survey (SF-36; general HRQL) and the Severe Respiratory Insufficiency (SRI) Questionnaire (condition-specific HRQL). In total, 85 (27 chronic obstructive pulmonary disease, 29 restrictive thoracic, 17 neuromuscular, nine obesity hypoventilation syndrome and three miscellaneous) out of 135 eligible patients completed the study. Mean+/-SD SRI summary scale (range 0-100) improved significantly and comparatively in all 85 patients from 49+/-15 at baseline to 61+/-15 at 1 month and to 61+/-16 at 1 yr, but improvements of subscale scores differed amongst subgroups. SF-36 scores also improved, but the SRI was superior in detecting HRQL changes. Facial soreness and dry throat were the most commonly reported side-effects. Patients spent a mean+/-SD of 12+/-6 days in hospital at baseline and 3+/-3 days at each follow-up visit. Only four patients required unplanned hospitalisation. Overall general and condition-specific health-related quality of life aspects improved following home mechanical ventilation establishment independent of the underlying disease, which, however, has an impact on changes within specific health-related quality of life domains. The need for hospitalisation is low once home mechanical ventilation is carefully established.