BACKGROUND Multiple breath washout (MBW) derived Scond is an established index of ventilation inhomogeneity. Time-consuming post hoc calculations of the expirogram's slope of alveolar phase III (SIII) and the lack of available software hampered widespread application of Scond. METHODS Seventy-two school-aged children (45 with cystic fibrosis; CF) performed 3 nitrogen MBW. We tested a new automated algorithm for Scond analysis (Scondauto ) which comprised breath selection for SIII detection, calculation and reporting of test quality. We compared Scondauto to (i) standard Scond analysis (Scondmanual ) with manual breath selection and to (ii) pragmatic Scond analysis including all breaths (Scondall ). Primary outcomes were success rate and agreement between different Scond protocols, and Scond fitting quality (linear regression R(2) ). RESULTS Average Scondauto (0.06 for CF and 0.01 for controls) was not different from Scondmanual (0.06 for CF and 0.01 for controls) and showed comparable fitting quality (R(2) 0.53 for CF and 0.13 for controls vs. R(2) 0.54 for CF and 0.13 for controls). Scondall was similar in CF and controls but with inferior fitting quality compared to Scondauto and Scondmanual . CONCLUSIONS Automated Scond calculation is feasible and produces robust results comparable to the standard manual way of Scond calculation. This algorithm provides a valid, fast and objective tool for regular use, even in children. Pediatr Pulmonol. 2015; 50:805-813. © 2014 Wiley Periodicals, Inc.