OBJECTIVE To determine the perinatal risk factors for pneumothorax in Very-Low-Birth-Weight (VLBW) infants and the associated morbidity and mortality in this population. METHODS Retrospective analysis of data collected prospectively from a cohort of VLBW neonates assisted in our Unit (2006-2013). We included all consecutive in-born patients with ≤ 1500 g, without severe congenital anomalies. Perinatal history, demographics, interventions and clinical outcomes were collected. Associations were evaluated by logistic regression analysis. RESULTS During the study period, 803 VLBW infants were assisted in our Unit, of whom 763 were inborn. Ten patients (1.2%) died in delivery room, and 18 (2.2%) with major congenital anomalies were excluded. Finally, 735 (91.5%) neonates were included in the study. Seventeen (2.3%) developed pneumothorax during the first week of life [median (IQR): 2 (1-2) days]. After correcting for GA and other confounders, prolonged rupture of membranes [aOR =1.002 (95% CI 1.000-1.003); p = 0.040] and surfactant administration [aOR = 6.281 (95% CI 1.688-23.373); p = 0.006] were the independent risk factors associated with pneumothorax. Patients with pneumothorax had lower probabilities of survival without major brain damage (MBD): aOR = 0.283 (95% CI = 0.095-0.879); p = 0.029. CONCLUSIONS Pneumothorax in VLBW seems to be related to perinatal inflammation and surfactant administration, and it is significantly associated with a reduction in the probabilities of survival without MBD.