Background Non-invasive ventilation (NIV) may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis (CF). Objectives To compare the effect of NIV versus no NIV in people with CF. Search strategy We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials. Most recent search: June 2008. Selection criteria Randomised controlled trials comparing a form of pressure preset or volume preset NIV to no NIV in people with acute or chronic respiratory failure in CF. Data collection and analysis Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Main results Fifteen trials were identified; seven trials met the inclusion criteria with a total of 106 participants. Six trials evaluated single treatment sessions and one evaluated a six-week intervention. Four trials (79 participants) evaluated NIV for airway clearance compared with an alternative chest physiotherapy method and showed that airway clearance may be easier with NIV and people with CF may prefer it. We were unable to find any evidence that NIV increases sputum expectoration, but it did improve some lung function parameters. Three trials (27 participants) evaluated NIV for overnight ventilatory support, measuring lung function, validated quality of life scores and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between NIV compared with oxygen or room air except for exercise performance, which significantly improved with NIV compared to room air over six weeks. Authors' conclusions Non-invasive ventilationmay be a useful adjunct to other airway clearance techniques, particularly in people with CF who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of NIV have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in CF airway clearance and exercise.