BACKGROUND: Despite the important role of MV in reducing mortality in very preterm infants, its use is often associated with complications. The study was aimed to determine the duration of mechanical ventilation (MV), which significantly increased the risk of adverse outcomes in very low birth weight (VLBW) infants. METHODS: Data obtained from a prospectively created computer database were used in a retrospective cohort study. The database included information about 1980 VLBW infants <32 weeks of gestation who were cared for at the tertiary care center between January 2010 and December 2020. RESULTS: Out of 1980 VLBW infants, 1086 (55%) were ventilated sometime during the hospital stay. 678 (62.43%) of ventilated babies survived until discharge. With ROC analysis, it was identified that MV duration of 60.5 hours had 79.3% sensitivity and 64.6% specificity for the prediction of BPD with the AUC of 0.784 (95% CI 0.733–0.827; p < 0.0001). The duration of MV above 60.5 hours was a significant risk factor for bronchopulmonary dysplasia (aOR 6.005, 95% CI 3.626–9.946), death (aOR 3.610, 95% CI 2.470–5.276), bronchopulmonary dysplasia/death (aOR 4.561, 95% CI 3.328–6.252), sepsis (aOR 1.634, 95% CI 1.168–2.286), necrotizing enterocolitis (aOR 2.606, 95% CI 1.364–4.980), and periventricular leukomalacia (aOR 2.191, 95% CI 1.241–3.867). CONCLUSIONS: Duration of MV longer than 60.5 hours is an independent risk factor for adverse outcomes in VLBW infants. It is essential to increase and optimize efforts to avoid MV or extubate very preterm infants as soon as possible, before reaching the established threshold duration of invasive respiratory support.