Objective To investigate the clinical effect of closed thoracic drainage with negative pressure drainage ball on neonatal pneumothorax. Methods From June 2021 to June 2022, a total of 44 children with pneumothorax undergoing thoracic closed drainage in the Neonatal Intensive Care Unit of our hospital were selected. According to different drainage methods, they were divided into a central venous catheter group （n=19, diameter 2.0-2.4 mm） and a negative pressure drainage ball group （n=25, diameter 5.3 mm）. The general condition, catheter placement time, drainage time, mechanical ventilation time, and the incidence of complications were compared between the two groups. Results There were no significant differences in sex, gestational age, birth weight, and lung compression ratio between the two groups （P>0.05）. In the negative pressure drainage ball group, the drainage time was （2.08±0.47） d, the hospital stay was （9.37±2.10） d, and the cure rate was 100.0%. In the central venous catheter group, the drainage time was （6.50±0.93） d, the hospital stay was （16.00±2.59） d, and the cure rate was 89.5%; all the differences of the indicators between the two groups were statistically significant （P<0.05）. There was a significant difference in the incidence of other postoperative complications between the two groups （P<0.05）, except 1 case of incision infection in the negative pressure drainage ball group. Conclusion The use of negative pressure drainage ball for thoracic closed drainage in the treatment of neonatal pneumothorax has a good drainage effect, shortens drainage time, is not easy to induce tube blockage, safe and effective, worthy of clinical application.