Introduction Objectively assessing pulmonary disease is challenging in preschool children with asthma. We evaluated the feasibility of measuring fractional exhaled nitrogen oxide (FeNO) and multiple breath nitrogen washout (N₂MBW) in children. We compared their capacities for discriminating between children with asthma and healthy controls. Methods We measured FeNO and N₂MBW-derived indices of lung clearance (LCI_2.5) and conductive and acinar ventilation heterogeneity (S_cond and S_acin) in 65 preschool children; 35 with physician-diagnosed asthma and 30 healthy. FeNO was measured with a portable device (sampling time, 6 s). We employed data quality control guidelines on N₂MBW. Feasibility was evaluated in a maximum of 8 attempts for both methods. Atopic co-morbidity and first-degree disposition were evaluated with the ISAAC-questionnaire. Results FeNO and N₂MBW testing were feasible in 45% and 91% of children, respectively. Feasibility was highly age-dependent. In children under 4 years old, FeNO was not feasible, but N₂MBW was 85% feasible. Children with asthma had significantly elevated S_cond values (median; 95% CI) (0.024; 0.020; 0.029) compared to healthy controls (0.019; 0.016; 0.023), but similar FeNO, LCI_2.5 and S_acinvalues. Conclusion The feasibility of measuring FeNO was highly age-dependent and not applicable in children under age 4. N₂MBW was feasible in the majority of preschool children. S_cond, but not FeNO, could discriminate between children with asthma and healthy controls.