BACKGROUND: Multiple-breath washout (MBW) is an established outcome measure of lung disease in cystic fibrosis (CF). However, data on its sensitivity to detect lung function impairment in bronchiectasis across age groups remain limited. The aim of this study was therefore to determine the feasibility, validity and sensitivity of MBW compared with spirometry in people with bronchiectasis. METHODS: We performed MBW and spirometry in 94 people with bronchiectasis (aged 0.2 to 79.3 years), 168 healthy controls, and 128 people with CF and 76 with asthma as disease controls. RESULTS: The overall success rate of MBW in all 466 participants was 96.1%. People with bronchiectasis had an elevated lung clearance index (LCI) and a reduced forced expiratory volume in 1 s (FEV(1)) compared with healthy controls and people with asthma (all p<0.001). Comparing bronchiectasis and CF, there was no difference in LCI, but FEV(1) was reduced in bronchiectasis (p=0.032). Within the bronchiectasis group, LCI correlated strongly with FEV(1) (r= -0.69, p<0.001). However, 34.3% of people with bronchiectasis presented with an elevated LCI but normal FEV(1), while none had a reduced FEV(1) combined with a normal LCI (p<0.001). LCI was superior to FEV(1) in detecting lung function impairment in bronchiectasis (area under the curve: 0.95 versus 0.86). CONCLUSION: LCI is more sensitive than FEV(1) to detect lung function impairment in bronchiectasis. These findings support further evaluation of LCI for clinical monitoring and as a sensitive outcome measure in clinical trials in people with bronchiectasis.