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Ventilator-associated pneumonia (VAP) is a highly common hospital-acquired infection affecting people that require mechanical ventilation. The endotracheal tube (ETT) used during the ventilation process provides a surface that can allow bacterial colonization and biofilm formation, which can lead to VAP. Although various approaches, including ETT design and material selection, as well as antimicrobial coatings have been employed to minimize adverse events, VAP remains a significant unresolved clinical issue. In this study, we have utilized a novel styrylbenzene-based antimicrobial (BCP3) in a simple and robust coating that allows its long-term release at an effective level. BCP3 was applied onto PVC ETT segments blended together with poly(lactic- co -glycolic acid) via a facile dip-coating process with controlled loadings. In vitro studies demonstrated concentration-dependent release of BCP3 from the coatings for at least 31 days. Bacterial assays using major VAP culprits, Staphylococcus aureus and Pseudomonas aeruginosa, demonstrated significant growth inhibition, with a stronger effect on S. aureus . Despite its ability to inhibit bacterial growth, BCP3 showed no cytotoxicity toward mammalian (L929) fibroblasts, which makes it attractive from a clinical perspective. The coating procedure was successfully translated to coat the entire ETTs, making it highly amenable for large-scale manufacturing., Competing Interests: The authors declare the following competing financial interest(s): The research described in the manuscript was supported by Boulos & Cooper Pharmaceuticals, which seeks to commercialize a range of novel antimicrobial compounds.The authors declare that Ramiz A. Boulos is a founder of Boulos & Cooper Pharmaceuticals., (Copyright © 2020 American Chemical Society.)