INTRODUCTION: FEV is often considered the gold standard to monitor lung disease in cystic fibrosis (CF). Recently, there has been increasing interest in multiple breath washout (MBW) and cardiopulmonary exercise testing (CPET) as alternative or even more sensitive techniques. However, limited data exist on associations among the above methods.AIM: To evaluate the correlations between outcome measures of MBW and CPET and to examine if ventilation inhomogeneity can predict exercise intolerance.SUBJECTS AND METHODS: Ninety-seven children and adults with CF (47 males, mean [range] age 14.9 (6.6; 26.7) years, mean FEV : 90.8% predicted, mean lung clearance index [LCI]: 11.4, and mean peak oxygen uptake [VO peak]: 82.4% predicted) performed spirometry, MBW, and CPET on the same day during their admission or outpatient visit.RESULTS: LCI, m /m , and m /m (P < 0.001) as well as VO peak%, breathing reserve (BR), minute ventilation (VE)/VO (P < 0.001), and VE/carbon dioxide release (VCO ) (P = 0.006) correlated significantly with FEV %. LCI, m /m , and m /m correlated with VO peak (P ≤ 0.001), VE (L/min) (P < 0.05), BR (P < 0.01), VE/VO (P < 0.001), and VE/VCO (P < 0.01). Multiple regression analysis showed that LCI could predict BR% (P < 0.001, r :0.272) and VE/VO (P < 0.001, r : 0.207) while LCI and FRC could predict VO peak% P < 0.001, r : 0.216) and VE/VCO (P < 0.001, r : 0.226).CONCLUSION: Ventilation inhomogeneity as indicated by increased LCI is associated with less efficient ventilation during strenuous exercise and negatively impacts exercise capacity in CF.