Fluid overload is common among pediatric cardiac patients receiving extracorporeal membrane oxygenation (ECMO) and is often treated with in-line ultrafiltration (UF) or continuous renal replacement therapy (CRRT). We assessed whether CRRT was associated with poor outcomes versus UF alone. Additionally, we identified characteristics associated with progression from UF to CRRT. Retrospective chart review of 131 patients age ≤18 years treated with ECMO at a single quaternary center. Data were collected to compare patient demographics, characteristics, and outcomes. A receiver operator curve (ROC) was used to create a tool predictive of the need for CRRT at the time of UF initiation. Patients who required CRRT had a higher creatinine and blood urea nitrogen at time of UF initiation (p = 0.03 and p < 0.01), longer total ECMO duration (p < 0.01), lower renal recovery incidence (p = 0.02), and higher mortality (p ≤ 0.01). Using ROC analysis, presence of ≤3 of 7 risk variables had a positive predictive value of 87.5% and negative predictive value of 50.0% for use of UF alone (area under the curve 0.801; 95% CI: 0.638–0.965, p = 0.002). Pediatric cardiac patients treated with ECMO and UF who require CRRT demonstrate worse outcomes versus UF alone. A novel clinical tool may assist in stratifying patients at UF initiation.