Impaired mucociliary clearance due to defective ion and water transport and the effects of chronic airway infections lead to stasis of secretions and progressive pulmonary damage in patients with cystic fibrosis (CF). Methods to improve removal of tenacious lung secretions in CF patients contribute to slowing the decline in respiratory function. We have evaluated an intrapulmonary percussive ventilator (IPV), which is a device designed to enhance airway clearance and preserve lung function. A previous pilot study by us had determined that the device was acceptable to patients and is safe. We undertook a 6 month parallel comparative trial of the IPV versus standard, manual chest physiotherapy in 16 CF children and adults. No significant differences in spirometric measures, numbers of hospitalizations, use of oral or IV antibiotics, or anthropometric measurements were detected between the standard aerosol/chest physiotherapy group and the IPV group over the duration of the trial. Patient acceptance, as determined by participant survey, was good. The device appeared to be safe and durable. It was concluded that the IPV is as effective as standard aerosol and chest physiotherapy in preserving lung function and anthropometric measures, and there was no difference in the use of antibiotics and hospitalizations.