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Asthma is one of the most common disorders of respiratory tract, management of which still remains as a serious health problem. This study aimed to compare the efficacy of 3% hypertonic saline (HS) plus salbutamol with solely salbutamol on management of acute adults' asthma based on peak flow meter findings. In this double-blind randomized clinical trial, 340 adult patients with acute asthma attacks admitted to emergency department of Ahvaz Golestan and Emam hospitals were enrolled during 2014-2015. The patients were allocated randomly to intervention group (nebulized 2.5 mg of salbutamol and 2.5 mL of 3% HS solution for three consecutive 20-min periods) and control group (nebulized only salbutamol in the same dose and time of the intervention group). The principal outcome measures were forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR), which were assessed at baseline, and 20, 40 and 60 minutes after treatment in both groups. HS plus salbutamol resulted in a significant increase compared with solely salbutamol in both PEFR and FEV1 in 40th min (0.11±1.36; p=0.036 and 0.05±1.16; p=0.033, respectively) and 60th min (0.15±1.12; p<0.001 and 0.11±1.22; p=0.011, respectively), while no significant difference was observed in baseline and 20th min. Also, PEFR and FEV1 in both groups significantly increased as the treatment processed and the time passed. The results showed the beneficial effects of 3% HS in management of adults with acute asthma in the short term.