AbstractNeonatal peripheral intravenous catheters (PIVCs) can be difficult to insert, often requiring multiple attempts, with each attempt causing pain and delaying treatment. The aim of this study was describe the clinical characteristics of neonates requiring multiple PIVCs during hospitalization. A secondary case series of neonates requiring three or more PIVCs during their admission were identified from a cohort admitted to an Australian Neonatal Unit between October 2020 and February 2021. Data were collected at PIVC insertion and removal; with variables including patient characteristics (weight, gestational age, acuity) and device characteristics (treatment indication, location), and outcomes (completion of treatment or failure). Outcomes are reported descriptively. In total, 19 of 248 (7.6%) neonates received three or more PIVCs (n = 101 PIVCs). Median gestation and weight were 26.6 weeks (interquartile‐range [IQR] 24.6–28.6 weeks) and 728 grams (IQR 640‐1050 g), respectively; all neonates required intensive care admission. The most common anatomical location was the hand (41.5%, n = 42). The maximum number of PIVCs required by a single patient was 12. The median dwell time was 49 h (IQR 35.0–73.5 h), with maximum dwell 263 h. In total, 57% (n=58/101 PIVCs) failed from complications, and 58% (n=59) of failed PIVCs required re‐insertion. Despite common clinician perceptions that large babies require more PIVCs, our results found extremely low birth weight babies required frequent cannulation, with many PIVCs failing prior to treatment completion. There is a need for further investigation regarding decision‐making, advanced inserter skills and optimization of alternate vascular access device selection for this vulnerable population. Clinical teams caring for neonates, particularly those of low birth weight and/or gestation, are recommended to take extra time considering the device they choose to insert, and the inserting clinicians. The aim of these recommendations is to reduce the number of treatment failures and device complications causing preventable treatment delays and ongoing injuries in neonatal critical care.