BackgroundCentral venous catheter (CVC)‐related complications remain a significant cause of morbidity in pediatric hematology‐oncology. We prospectively surveyed the incidence of CVC‐related complications in children with hematologic‐oncologic diseases.ProcedureFive‐hundred‐eighty‐one CVCs were inserted in 421 patients from January 2010 to June 2022 (153,731 CVC days observation; follow‐up data up to December 31, 2022).ResultsOverall, 671 complications were recorded (4.365/1000 CVC days): 49.7% malfunctions (1.88/1000 CVC days, 4.8% of CVC early removals), 23.9% bacteremia (0.90/1000, 15.1%), 19.6% mechanical complications (0.74/1000, 70.2%), 20.1% localized infections (0.76/1000, 17.1%), 0.5% thrombosis (0.02/1000, 33.3%). At multivariate analysis, risk factors for malfunction were Broviac–Hickman type of CVC (hazard ratio [HR] 2.5) or Port‐a‐cath (HR 3.4) or Proline (HR 4.3), p < .0001; for bacteremia double‐lumen CVC (HR 3.2, p < .0001); for mechanical complications age at CVC insertion under median (HR 4.5, p < .0001) and Broviac–Hickman (HR 1.6) or Proline (HR 2.7), p = .01; finally for localized infections Broviac–Hickman (HR 2.9) or Proline (HR 4.4), p = .0001. The 2‐year cumulative incidence of premature removal was 23.5%, and risk factors were age at CVC insertion under median (HR 2.4, p < .0001), Broviac–Hickman (HR 2.3) or Proline (HR 4.2), p < .0001.ConclusionsPremature removal occurs in approximately 20%–25% of long‐term CVCs. A surveillance program has a fundamental role in identifying the risk factors for CVC complications and the areas of intervention to improve CVC management.