Acute bronchiolitis is a common, potentially life-threatening condition with few therapeutic options. In the present randomized study, we compared the clinical efficacies of nebulized epinephrine and salbutamol in the emergency room management of acute bronchiolitis. Primary outcome measures were improvement in mean respiratory rate, mean oxygen saturation value and severity score. Secondary outcome measures were length of hospital stay, hospitalization and relapse rates. A total of 75 patients were analyzed (36 epinephrine, 39 salbutamol). Both groups experienced a similar pattern of clinical improvement. Hospitalization rates were 8.3% for epinephrine and 5.1% for salbutamol (p > 0.05), whereas relapse rates were 80% for epinephrine and 20% for salbutamol groups (p < 0.001). Respiratory syncytial virus was the most common virus identified (41%). We did not find a difference between salbutamol and epinephrine in terms of clinical improvement, but salbutamol can be a drug of choice due to its lower relapse and hospitalization rates compared to epinephrine.