Weaning from invasive mechanical ventilation and the ideal time for extubation of preterm newborns (PTNBs) should be performed early. However, the ideal time to perform them is still a challenge in neonatal intensive care unit (NICU). The aim of the study was to present the ventilatory profile of premature infants submitted to invasive mechanical ventilation, assess the extubation failure rate and the elaboration of an extubation protocol. Methods: This was a descriptive cross-sectional study carried out in an NICU with PTNBs who underwent invasive mechanical ventilation for a period longer than 24 h. Results: Twenty-seven PTNBs participated in this study, from which 43 extubation events originated. The overall extubation failure rate observed in the study was 23.3%, being higher among PTNBs younger than 28 weeks (50%). Regarding the failure rates according to birth weight ranges, extremely low weight PTNBs (less than 1,000 g) had the highest rates, followed by very low weight PTNBs (1,000 g to 1,499 g), with rates of 33.3% and 21.4%, respectively. Conclusions: Knowing the ventilatory profile of PTNBs and the risk factors associated with extubation failure facilitates the weaning process and increases the chance of successful extubation.