BACKGROUND AND AIMS: Inhalation of hypertonic saline (HTS) has short term positive effects on airways clearance in non-cystic fibrosis (CF) bronchiectasis, however its long term effects are unknown. The aim of this study was to determine the effect of HTS 6% on exacerbations, quality of life (QOL) and respiratory function over 12 months in non-CF bronchiectasis. METHODS: Forty patients were randomised to inhale isotonic saline (IS) 0.9% or HTS 6% daily for 12 months. Participants recorded their symptoms in a daily diary. Quality of life and respiratory function were measured after three, six and 12 months. Number of exacerbations and changes in sputum colonisation were recorded at 12 months. Participants, assessors and clinicians were blinded to group allocation. RESULTS: The exacerbation rate at 12 months was similar in the two groups and similar clinically significant improvements in QOL were seen in both groups. The FEV(1) increased in both groups after six months (mean 90 ml, 95% confidence interval 11-169 ml) with no difference between groups (p = 0.394). The FEF(25-75%) significantly improved at all time points (mean increase at 12 months 187 ml, 69-304 ml) with no difference between groups (p = 0.705). There was a reduction in sputum colonisation in both groups (p = 0.046). CONCLUSIONS: Inhalation of HTS or IS has similar effects on exacerbations, QOL, sputum colonisation and respiratory function over 12 months in non-CF bronchiectasis. The trial was registered with both Clinical Trials.gov - NCT00484263 and Australian New Zealand Clinical Trials Registry - ACTRN12607000367448.