Jet nebulization (JN) and non-invasive mechanical ventilation (NIMV) through bi-level pressure is commonly used in emergency and intensive care of patients experiencing an acute exacerbation of asthma. However, a scientific basis for effect of JN coupled with NIMV is unclear. Objective. To evaluate the effect of jet nebulization administered during spontaneous breathing with that of nebulization with NIV at two levels of inspiratory and expiratory pressures resistance in patients experiencing an acute asthmatic episode. Methods. A prospective, randomized controlled study of 36 patients with severe asthma (forced expiratory volume in 1 second [FEV(1)] less than 60% of predicted) selected with a sample of patients who presented to the emergency department. Subjects were randomized into three groups: control group (nebulization with the use of an unpressured mask), experimental group 1 (nebulization and non-invasive positive pressure with inspiratory positive airway pressure [IPAP] = 15 cm H(2)O, and expiratory positive airway pressure [EPAP] = 5 cm H(2)O), and experimental group 2 (nebulization and non-invasive positive pressure with IPAP = 15 cm H(2)O and EPAP = 10 cm H(2)O). Bronchodilators were administered with JN for all groups. Dependent measures were recorded before and after 30 minutes of each intervention and included respiratory rate (RR), heart rate (HR), oxygen saturation (SpO(2)), peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), and forced expiratory flow between 25 and 75% (FEF(25-75)). Results. The group E2 showed an increase of the peak expiratory flow (PEF), forced vital capacity (FVC), FEV(1) (p < 0.03) and F(25-75%) (p < 0.000) when compared before and 30 minutes after JN+NIMV. In group E1 the PFE (p < 0.000) reached a significant increase after JN+ NIMV. RR decreased before and after treatment in group E1 only (p = 0.04). Conclusion. Nebulization coupled with NIV in patients with acute asthma has the potential to reduce bronchial obstruction and symptoms secondary to augmented PEF compared with nebulization during spontaneous breathing. In reversing bronchial obstruction, this combination appears to be more efficacious when a low pressure delta is used in combination with a high positive pressure at the end of expiration.