Background: The objective of this study is to investigate the efficacy of continuous renal replacement therapy (CRRT), mainly continuous venovenous hemodiafiltration (CVVHDF), and evaluate vasoactive requirements in hyperammonemic neonates and infants. Methods: Patients who underwent CRRT for hyperammonemia were retrospectively analyzed. Measurements and Main Results: Patients in 7 of the encounters were treated solely by CVVHDF. During 3 encounters, patients who received continuous venovenous hemodialysis (CVVHD) were transitioned to CVVHDF. CVVHD was used in 3 encounters. The median 50% reduction time for ammonia was 8 h (range 3-15 h). The median duration of CRRT treatment was 40 h (range 24-89 h). Survival to hospital discharge occurred in 12 encounters (92.3%). Eleven encounters (84.6%) were treated with different vasoactive agents. In those encounters, the median vasoactive medications' start time was the 6th hours (range 2-60 h) of CRRT. There was no association between the vasoactive index score and pre-dialysis ammonia concentration. Conclusions: CRRT achieves timely control of hypeammonemic states. Hemodynamic instability necessitating intervention with vasoactive medications is a common finding in patients with hyperammonemia.