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Aim Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals.\ud \ud Methods Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as ‘fit’ for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes.\ud \ud Results A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0−95, 95% CI: 0.75−1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76−1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation.\ud \ud Conclusion This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings.\ud \ud ClinicalTrials.gov registration number NCT01469845.