A multicenter trial compared intermittent positive pressure breathing (IPPB) therapy with compressor nebulizer therapy in 985 ambulatory patients with chronic obstructive pulmonary disease. A bronchodilator aerosol solution was administered with both treatments, the only difference being the positive pressure applied by IPPB. Patients were randomly assigned to treatment and closely followed by monthly home and quarterly clinic visits for an average of 33 months. Compliance with treatment, lung function, and quality of life were evaluated at regular intervals during follow-up, and records were kept of hospitalizations and vital status. Treatment compliance was disappointing; only half of the patients used their devices the prescribed amount of time. There was no statistically significant difference between the treatment groups in mortality, rate and duration of hospitalizations, or change in lung function or life quality with time, overall or for clinically relevant subgroups. We saw no advantage of IPPB over compressor nebulizer therapy in this large group of patients, and conclude that, if an advantage exists, it must be marginal.