The aim of this study was to evaluate long-term efficacy and tolerance of nasal mask ventilation (NMV) in a comparative case-control study. Fourteen patients with diffuse bronchiectasis and severe chronic respiratory failure (CRF), treated by long-term oxygen-therapy (LTO) and NMV, were case matched with 14 patients with diffuse bronchiectasis and severe CRF treated with only LTO. Patients and control subjects were compared based on the following parameters: blood gases, FEV1, vital capacity, hospitalizations, and survival. Symptoms, Karnofsky function score, and clinical evolution were also monitored in patients. Three subgroups may be identified according to outcome: two early deaths (subgroup 1), six patients with initial improvement and subsequent deterioration (subgroup 2), and six patients whose conditions remained improved for >2 years (subgroup 3). PaO2 decrease slope was slighter in this last subgroup than subgroup 2. The days of hospitalization were significantly reduced after institution of NMV in the patient group. Comparison between patients and control subjects did not show any difference on PaO2 evolution and on the overall median survival (46 and 40 months in NMV and control group, respectively). Long-term tolerance and compliance remained satisfactory for 11 patients. These results suggest that NMV is feasible as a long-term home treatment in patients with diffuse bronchiectasis. Although our results may have failed to prove a long-term efficiency on the course of blood gases and survival, a beneficial effect is observed with reduction of hospitalizations and improvement of functional status. This study warrants further investigation, in a prospective series, with a larger number of patients.