Introduction: Continuous venovenous haemodiafiltration is an extracorporeal blood purification technique that can be used in the treatment of metabolic diseases. The aim of this study was to evaluate its effectiveness and complications in the treatment of metabolic decompensation in patients with inborn errors of metabolism. Methods: Cases in which heaemodiafiltration was used in a paediatric intensive care unit over 10 years were reviewed. Results: We performed 18 sessions of continuous venovenous haemodiafiltration in 15 patients (10 with maple syrup urine disease, five with hyperammonaemia); 11 of the sessions were in newborns. The technique was initiated because of severe metabolic decompensation with neurological signs in 10/18 cases, within the first six hours of hospitalization. The median technique duration was 18 hours. There was a significant reduction in levels of leucine (1940 µmol/l to 400 µmol/l) and ammonia values (1433 µmol/l to 255 µmol/l) (p ≤ 0.01). In three cases, haemodiafiltration was suspended because of serious bleeding complications. Three types of vascular access (jugular, femoral and umbilical) were used. Jugular access resulted in longer filter life (p = 0.002). The mean length of hospital stay was 4.9 days; patients required invasive ventilation in 13 episodes. The survival rate was 66.7%. Discussion: The success of continuous venovenous haemodiafiltration in the treatment of acute metabolic decompensation is reported. The technique was very effective in reducing toxic metabolites, but the complexity of these patients and the possibility of fatal complications demonstrates the need for careful patient selection and experience in implementation. Jugular access appears to be best for this technique.