Hospital-acquired infections (HAIs) pose a significant and increasing threat to global health. One primary cause of this threat is increasing antibiotic resistance. As traditional antibiotics continue to grow less effective, there is an urgent need for novel antimicrobial strategies. This work explores the potential of ceragenins, also known as cationic steroid antimicrobials (CSAs), as a promising alternative to combat HAIs. Specifically, we investigated potential roles that CSAs can play in the context of multiple medical device coatings in healthcare settings. Ceragenins are synthetic mimic of antimicrobial peptides (AMPs) which exhibit broad-spectrum antimicrobial activity against many common pathogens that have been cited as high priority by global health organizations. Unlike traditional antibiotics, which rely on specificity to bacterial enzymes or processes, ceragenins disrupt microbial membranes generally. This mechanism of action allows ceragenins to bypass many of the related antibiotic resistance mutations of bacteria and fungi. As microbial membranes are a highly conserved and fundamental structure of these pathogens, it is much more difficult for microbes to develop mutations that prevent CSA binding. Additionally, ceragenins are resistant to both host and pathogenic proteolytic degradation and are cost-effective to produce, which place CSAs as an attractive alternative to traditional antibiotics. This research investigates the integration of ceragenins into various medical devices to prevent HAIs. Specifically, we investigated silicone tissue expanders, peripherally inserted central catheter (PICC) lines, and adhesive devices which include both polyacrylate and silicone scar tape. These studies include the development of coating techniques to maximize appropriate antimicrobial activity while maintaining stability and biocompatibility across these different base materials. Our experimental results demonstrate that ceragenin-coated devices significantly reduce microbial colonization and biofilm formation. We considered the length of antimicrobial activity needed and developed coatings that would be appropriate for those use cases. This reduction in harmful pathogenic colonization demonstrates their potential to improve patient outcomes and reduce healthcare costs associated with HAIs. Further research and development could facilitate the continued adoption of ceragenin-based coatings in medical devices, which can reduce the incidence of HAIs while contributing to the broader fight against antibiotic-resistant infections worldwide.