To determine the significant risk factors associated with development of chronic lung disease (CLD) in Malaysian very low birthweight (VLBW, < 1501g) infants. A prospective observational study was carried out at the Sarawak General Hospital (SGH) in Kuching, over a period of 29 months from 1 April 2003 to 31 August 2005. Infants with birthweight between 600g to 1500g admitted to this hospital were recruited. The progress of these infants was followed till discharge. CLD was defined as the persistent need for oxygen therapy to maintain oxygen saturation above 88% at 36 weeks of postmenstrual age. Of the 224 infants recruited, 36 (14.8%) had CLD. Logistic regression analysis showed that lower birth weight (adjusted odds ratio (OR) = 0.996, 95% confidence intervals (CI) = 0.994, 0.998; p = 0.001), male infants (adjusted OR = 3.9, 95% CI = 1.6, 11.7; p = 0.02), chorioamnionitis (adjusted OR = 9.0, 95% CI = 1.6, 50.8; p = 0.01), severe respiratory distress syndrome of grades 3 or 4 (adjusted OR = 4.6, 95% CI =1.6, 13.2; P = 0.005) and patent ductus arteriosus (adjusted OR = 4.3, 95% CI = 1.5, 12.8; p = 0.007) were significant risk factors associated with development of CLD. A number of treatable conditions are associated with development of CLD in Malaysian VLBW infants.