Background/Objective: Air leak syndromes are frequent in neonatal period. mechanical Ventilation with positive pressure is one of the most common causes of these syndromes. The aim of this study was to detect the incidence of pneumothorax in newborns under mechanical Ventilation.Patients and Methods: This descriptive cross sectional study was performed on 400 newborns admitted in the intensive care unit of 22 Bahman Hospital of Mashhad during 1383-1387. All patients were under mechanical Ventilation. Sex, gestational age, birth weight, type of delivery, history of surfactant therapy and mortality rate after pneumothorax were recorded in questionnaires. Statistical analysis was done on the obtained data using SPSS software.Results: Among 400 patients under Ventilation, 102 neonates developed pneumothorax (26%). 55% of these cases were boys and 45% were girls. Pneumothorax was on the right side in 66.7%, on the left side in 12.8% and bilateral in 19.6%. In newborns with pneumothorax 54.9% were preterm and 45.1% were term. Birth weight less than 2500g was seen in 59.8% of the cases. Among these neonates 19.6% were very low birth weight (under 1500g). In newborns with pneumothorax, 52% were born with cesarean section and 48% with normal vaginal delivery which was significantly different (P= 0.015). Surfactant therapy was recorded in 32.4% of cases with pneumothorax. The most common type of Ventilation leading to pneumothorax was Synchronized Intermittent Mandatory Ventilation (SIMV) in 51%, Conventional Ventilation and Continious Positive Airway Pressure (CPAP) were seen in 35% and 12.3% of pneumothoraces, respectively. Conclusion: Male sex, prematurity, birth weight below 2500g, cesarean section, negative history of surfactant therapy were risk factors of neonatal pneumothorax. CPAP was the least common kind of Ventilation in pneumothorax cases.