Background: Acute kidney injury (AKI) frequently occurs in neonates and infants after cardiopulmonary bypass (CPB) and may require renal replacement therapy (RRT). Peritoneal dialysis (PD) is the RRT modality of choice in neonates with AKI after CPB, but continuous renal replacement therapy (CRRT) may be necessary if PD is ineffective or contraindicated. Vascular access is challenging in this population, in part, due to small central vein size that may preclude placement. The risk of malfunction or morbidity associated with standard dialysis catheters may be excessive in neonates with congenital heart disease. We describe a unique approach to vascular access for CRRT in six small patients with AKI. Case-Diagnosis/Treatment: This is a retrospective review of six patients with fluid overload and AKI that received CRRT because PD was contraindicated. In all cases, CRRT was performed via two hemostasis valve sheaths placed into separate veins for dialysis access and return. The low-resistance sheaths provided excellent blood flow with normalization of metabolic derangements and significant fluid removal (median negative 167 ml/kg at 72 h). Mean circuit life before the first change was 55.2 ± 30.4 h. Conclusions: The use of two small single-lumen catheters in separate veins enables consistent and effective hemodiafiltration in neonates and infants with challenging vascular access. © 2013 IPNA.