OBJECTIVES: Cystic fibrosis (CF) is the most common fatal genetic disease in Caucasians with an annual birth incidence of 1:2,500. CF is ultimately fatal due to progressive dysfunction of organs such as lung and pancreas.  Improved knowledge of the ion channel defect that causes the disease has raised the possibility of treating the cause of CF. To develop an understanding of how different factors contribute to disease progression, published evidence was used to develop a model of mortality as a function of age and prognostic factors. METHODS: A systematic literature review of CF disease progression was performed in Medline and Embase. Prospective and retrospective cohort studies as well as case-control studies were included if they reported mortality jointly with prognostic factors. Covariates of interest included gender, lung function, weight-for-age, pancreatic sufficiency, diabetes, lung microflora and number of acute exacerbations. Results were synthesized by means of Bayesian meta-analysis techniques. RESULTS: Seven studies provided data on over 22,000 patients, which helped to develop a survival model based on age and the prognostic factors.  Survival over time was described with a Gompertz model with its scale parameter affected by birth cohort, gender, lung function, infection with Burkholderia cepacia and Staphylococcus aureus, diabetes, number of exacerbations, and pancreatic sufficiency. The shape parameter was assumed to be only affected by birth cohort. CONCLUSIONS: A survival model was developed that estimates remaining life expectancy for CF patients based on their clinical characteristics. Lung function is the primary determinant of life expectancy, but several other factors have major impact.  Of these, lung function and acute exacerbations are direct targets of intervention, while infections may be prevented or treated, and diabetes and pancreatic insufficiency may be methodically managed to potentially improve survivorship.