Epicutaneo-caval catheters (ECC) are vital in neonatal intensive care units (NICU) in enabling prolonged venous access. Despite their benefits, central line-associated bloodstream infections (CLABSI) pose a potential risk. The ECC removal procedure may contribute to an increased risk of post removal sepsis through biofilm release. Antimicrobial-impregnated ECCs have been proposed as a potential solution to prevent this complication, but research on their effectiveness in neonates is limited. To compare post-ECC or neonatal peripherally inserted central catheter (n-PICCs) removal sepsis rates when using conventional or antimicrobial-impregnated catheters in neonates. A retrospective, single center cohort analysis using 2019 data from 421 neonates after successful ECC insertion at the Women's Wellness and Research Center, a large tertiary level NICU in Qatar. The study systematically collected data on demographics, insertion, and removal as well as microbiology, and infection data. Statistical analyses compared conventional and antimicrobial ECCs, with a focus on the incidence of sepsis within 72 hr post-removal. After excluding non-eligible, 349 cases were included in the analysis (138 conventional, 211 antimicrobial-impregnated). There were no significant demographic differences between the two groups. The CLABSI incidence was higher amongst the antimicrobial ECC group (4% vs 0.6%, p = 0.031). Among the included neonates, the confirmed post-removal sepsis incidence was 4.3% (6 cases) for the conventional and 10% (21 cases) for the antimicrobial ECC groups, which was not statistically significant (p = 0.055). The study noted a higher, but statistically insignificant, incidence of post removal sepsis when using antimicrobial-impregnated ECCs. This finding raises questions about the effectiveness of antimicrobial ECCs in preventing post-removal sepsis in this patient population. Further randomized trials are needed to assess the role of antimicrobial ECCs amongst neonates and to refine neonatal ECC care strategies.