Mechanical ventilation is the primary treatment for preterm infants with respiratory failure. Prolonged intubation may lead to complications; thus, early extubation is desirable. No standard criteria exist for determining the appropriateness of extubating very-low-birth-weight (VLBW) infants. This study explored the predictors of successful extubation in preterm VLBW infants. This retrospective cohort study included 60 preterm VLBW infants who underwent their first extubation in the neonatal intensive care unit in a regional hospital in Hsinchu, Taiwan, between January 2017 and November 2020. Successful extubation was defined as having no requirement of reintubation within 3 days of extubation. Potentially predictive variables, including demographics, prenatal characteristics, and ventilator parameters were compared between a successful extubation group and failed extubation group. Of the 60 infants, 47 (78.33%) underwent successful extubation. The successful extubation group had higher Apgar scores at 1 (7 vs. 6, P=0.02) and 5min (9 vs. 7, P=0.007) than those of the failed extubation group. Ventilator inspiratory pressure and mean airway pressure were significantly lower at 24, 16, 8, and 1h before extubation and upon its completion in the successful extubation group. The areas under a number of the receiver operating characteristic curve curves in this study were moderate, specifically, 0.72, 0.74, and 0.69. Statistical analysis revealed an association between ventilator parameters before 1h extubation (IP>17.5cmH2O, MAP >7.5 cmH2O, RSS >1.82) and extubation failure (odds ratio 1.73, 2.27, 2.46 and 95% confidence interval:1.16-2.6, 1.26-4.08, 1.06-5.68, respectively). Higher Apgar scores at birth, lower ventilator inspiratory pressure, and mean airway pressure 24, 16, 8, and 1h and 1h RSS prior to extubation are associated with successful extubation in VLBW preterm infants.