Background The ability of clinicians to predict successful extubation in mechanically ventilated premature neonates is limited. Identifying objective criteria for predicting successful extubation may reduce the incidence of failed extubation and the duration of mechanical ventilation. Objective To evaluate the validity of objective measures of lung function and spontaneous breathing trial (SBT) in predicting successful extubation among premature neonates with attempted extubations within the first 3 weeks of life. Methods Respiratory compliance (Crs) along with SBT was performed prior to elective extubations within 3 weeks of age in premature infants ≤32 weeks. Extubation was considered successful if patients remained extubated for >72 hr. Ventilator settings including mean airway pressure (MAP), set rate, and fraction of inspired oxygen (FiO2) 24 hr after re-intubation were compared with pre-extubation settings, in patients requiring re-intubation. Results Thirty-nine of 49 infants (80%) were successfully extubated. Of 41 babies who passed SBT, only 5 infants failed extubation. SBT had 92% sensitivity, 50% specificity, 88% positive predictive, and 63% negative predictive value for successful extubation. Crs was comparable between infants who were successfully extubated and those who were not. Conclusions A SBT prior to extubation may be a practical objective adjunct in predicting successful extubation in ventilated premature infants.