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Background While cardiopulmonary transition in neonates is well described, molecular changes which accompany it are not. The Extracellular Vesicles in Early preterm neonates and Thrombin generation (EVENT) study sought to explore molecular transition in preterm birth. How this differs from term-born neonates is not well described.Methods A post hoc evaluation of proteomic data generated from a subset of the prospective, single site observational EVENT study was performed comparing extracellular vesicle enriched plasma from term neonates (n=10) with preterm neonates (n=20) using a mass spectrometry, data dependent acquisition-based proteomic approach. Bioinformatics was performed using MaxQuant proteomics software and R statistical software.Results Substantial differences were found between the preterm and term extracellular vesicle proteome, with proteins involved in extracellular matrix biology, immune function and embryogenesis all differentially expressed. Preterm neonates could be identified by their proteomic profile alone, reflecting their distinct physiology.Conclusions These protein expression differences may underlie the pathogenesis of complications of prematurity, such as bronchopulmonary dysplasia, retinopathy of prematurity and intraventricular haemorrhage.