OBJECTIVE This study aimed to determine the risk factors associated with the development of pneumothorax among infants admitted to the Malaysian neonatal intensive care units (NICUs). METHODS Twenty-nine of forty NICUs in Malaysian public hospitals participated in the 2006 Malaysian National Neonatal Registry (MNNR). Data of infants from this registry with and without pneumothorax were analysed. A diagnosis of pneumothorax was made in the presence of extra-pleural air detected by chest radiograph or needle aspiration. RESULTS There were 10,387 infants admitted to these NICUs who met the MNNR inclusion criteria and were included in this study. Pneumothorax developed in 505 (4.9%) of them. Pneumothorax was most common (7.3%) among the extremely low birthweight infants (birthweight equal or less than 1000 g) and the extremely preterm infants of gestation equal or less than 26 weeks (6.8%). Logistic regression analysis showed that the significant risk factors associated with increased risk of development of pneumothorax were: meconium aspiration syndrome (adjusted odds ratio (OR) = 2.1, 95% confidence intervals (CI): 1.7, 2.7), intermittent mandatory ventilation (adjusted OR = 1.5, 95% CI: 1.2, 2.0), high-frequency oscillatory ventilation (adjusted OR = 3.9, 95% CI: 3.0, 5.2) and confirmed sepsis (adjusted OR = 1.6, 95% CI: 1.3, 2.1). Infants on nasal continuous positive airway pressure (nCPAP) therapy were associated with significantly lower risk of pneumothorax (adjusted OR = 0.5, 95% CI: 0.4, 0.6). CONCLUSIONS Meconium aspiration syndrome, mechanical ventilation and sepsis were associated with increased risk and the use of nCPAP with decreased risk of pneumothorax in Malaysian NICUs.