Abstract: Clinical materials of two children with pleural effusion after peripherally inserted central catheterization in neonatal intensive care unit of our hospital in 2019 were analyzed retrospectively. Two cases were premature infants, and they were conducted with peripherally inserted central catheterization (PICC) after birth. Progressive dyspnea occurred after catheterization in two cases, and bedside chest X-ray and ultrasound indicated right pleural effusion. Dyspnea improved after immediate extubation of peripherally inserted central catheterization and one time thoracic puncture drainage, and no pleural effusion occurred. They were discharged smoothly on the basis of routine treatments. The results suggested that unexplained progressive dyspnea after peripherally inserted central catheterization in neonates might consider the possibility of pleural effusion, and the central venous catheter should be removed immediately after definite diagnosis.