Background We have previously modelled future trends in CF demography by calculating flows of patients entering and exiting CF cohorts (Burgel et al. Eur Resp J 2015). These forecasts, which were based on the assumption that major demographic trends remained stable over time, suggested a major increase in the number of CF adults in western European countries by 2025. Objectives To examine the effects of large variations in CF mortality or incidence on estimated numbers of CF patients. Methods Using the flow method on data from the French CF Registry from 2003 to 2012, we estimated numbers of CF children and adults by 2025 (main analysis). Because this analysis assumed that flows remained stable, we examined the impact large variations in CF incidence or mortality on future numbers of CF patients. Results In 2012, there were 6145 CF patients (3099 children; 3046 adults) in the French CF Registry. Applying average flows to these data, the number of CF patients will increase to 8344 patients (3534 children; 4810 adults) by 2025. Assuming a 50% decrease in pediatric and adult mortality, the number of CF patients in 2025 will increase to 8911 patients (+567 patients; +7%) including 3601 children (+67 children; +2%) and 5310 adults (+500 adults; +10%) as compared with the main analysis. Assuming a decrease in CF incidence by 30%, the estimated number of CF patients in 2025 will be 7969 patients (–375 patients; –4%) including 3159 children (–442 children; –12%) and 4810 adults (unchanged). Conclusion Large variations in CF mortality or incidence would have only minimal impact on the major increase in the number of CF adults that is expected in France by 2025.