Background/Purpose: Continuous renal replacement therapy (CRRT) is difficult in neonates for several reasons, including problems with catheter placement and maintenance. We sought to compare outcomes between standard hemodialysis catheters (HDC) and 6Fr-tunneled central venous catheters (TC-6Fr). Methods: We evaluated neonates who received CRRT from December 2013 – January 2018. All patients received CRRT with the Aquadex (Baxter Corporation, Minneapolis, Minnesota) circuit. Data regarding patient demographics, CRRT indication, catheter days, reason for removal, and catheter-specific complications were analyzed. Results: Forty-six catheters were placed in 26 neonates; nine of these were 6Fr-tunneled catheters. The median age and mean weight at CRRT initiation was 9.5 days (IQR 4–31) and 3.5 kg (+/- 0.6 kg), respectively. TC-6Fr lasted longer (median of 28 days vs 10 days, p = 0.02), required fewer revisions (0 vs 0.16/10 catheter days) and were less commonly removed due to bleeding complications (0% vs 10.8%), occlusion (11.1% vs 18.9%), or malposition (0% vs 8.1%); none of these differences were statistically significant. TC-6Fr were associated with higher infection rates (33.3% vs 0%, p = 0.01) than HDC. Conclusions: TC-6Fr use resulted in less need for catheter revisions and provided longer-lasting vascular access, which may influence infection rates. This catheter provides neonates in need of CRRT more reliable vascular access. Level of evidence: : III.