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Introduction:<b> </b>In neonatal intensive care units (NICU), inserting a peripherally inserted central venous catheter (PICC) is becoming an essential technique. Therefore, assessing the prevalence and risk factors of PICC line-related complications was the aim of this study.Methods: A retrospective observational cross-sectional study was carried out in Neonatal Intensive Care Unit during the period of 2012 to 2019 at King Fahd Hospital of the University (KFHU), Khobar, Saudi Arabia. A total of 120 neonates were included. PICC line-related complications including infection, thrombosis, occlusion, leakage, pericardial effusion, and neonatal death were collected from the medical records. While risk factors for PICC line-related complications were assessed using chi-squared test.Results:PICC complications occurred in 28 (23.3%) of cases among 120 PICCs. The incidence of proven infection was (11.7%), leakage (10%), local infection (4.2%), thrombosis (0.8%), and no death. The rate of complications was higher among neonates with low gestational age (24-26 weeks), neonates with extremely low birth weight, neonates who stayed for 30 days or more, and neonates with older age days (aged 10-14 days).Conclusion:Findings from this study showed that one out of each five neonates with PICC at NICU experienced a PICC line related complication, with infections and leakage being the most encountered complications. In current study, PICC line related complications had a significant association with neonatal birth weight, gestational age, and length of stay.