Introduction: Aerosol therapy using a metered‐dose inhaler (MDI) coupled to a spacer chamber is the most widely used long‐term treatment modality for chronic lung disease of prematurity. However, its use in neonates is based on data obtained from other age groups. Proper use of maintenance treatment is essential for the long‐term stability of these patients. Objective: To ascertain whether newborns are capable of generating negative pressure during the use of a spacer with face mask for aerosol therapy. Patients and methods: Total of 117 low‐risk newborns (age 12‐48 hours), with no congenital malformations or any detectable clinical symptoms, were included. Inspiratory pressure was measured with a respiratory pressure meter, at each respiratory cycle, during a 10‐second period, for three sequential measurements. The meter was connected to the inner chamber of the spacer through a noncollapsible silicone tube. Suitably sized masks were used. Results: Only 43 participants (36.8%) generated a negative pressure capable of opening the spacer valve, as verified by the respiratory pressure meter. In 25 patients, all three measurements were within the expected range. Weight, gestational age, and mode of delivery were in no way associated with the ability to generate a detectable negative pressure. Conclusion: In neonates, the MDI therapy with a spacer chamber and face mask is susceptible to failure due to the inability of most patients in this age range to generate a negative inspiratory pressure sufficient to open the spacer valve.