Background: Tissue nitrogen impacts the calculation of multiple breath nitrogen washout (MBW N2 ) outcomes. The aim of this study was to apply correction equations for tissue N 2 excretion to the functional residual capacity (FRC) and lung clearance index (LCI) derived from MBW N2 . Methods: MBW N2 measurements from 35 subjects with CF and 43 healthy controls were collected using an Exhalyzer D device (EcoMedics, Switzerland) and corrected breath-by-breath for the contribution of tissue N 2 using equations proposed by Cournand, A et al. 1941. Turnover value was calculated at sequential normalized end-tidal N 2 concentrations of 2.5%, 5%, 9%, 12%, and 18%. FRC was also measured by plethysmography (FRC pleth ). Results: Subjects were on average 16.4 (SD 6.8) years old with LCI ranging from 5.9 to 19.3. FRC MBW was greater than FRC pleth in health (mean difference 0.2 L (95% CI 0.1 to 0.3, p MBW values in healthy subjects closer to FRC pleth (mean difference 0.1 L (95% CI 0 to 0.2, p=0.02)). The uncorrected LCI was significantly greater than the corrected LCI in both health (mean difference 0.4 (95% CI 0.3 to 0.4, p 2 excretion on both FRC and LCI increased significantly with longer washouts. Conclusions: Application of a tissue N 2 correction or use of earlier washout cut-offs could reduce the influence of tissue N 2 on MBW N2 outcomes. Funding: Seller9s Chair for Cystic Fibrosis, Irwin Family Foundation.