Nonketotic hyperglycinemia (NKH) is a devastating inborn error of glycine metabolism caused by deficient activity of the glycine cleavage enzyme. Classically, patients present with lethargy, hypotonia, myoclonic jerks, transient respiratory depression in the first week of life and often progress to death. Surviving infants have profound psychomotor retardation, refractory epilepsy and poor quality of life. Currently, no effective therapeutic avenues exist for severe NKH. Ketogenic diet (KD) has been trialled only in a small group of patients with neonatal NKH and early myoclonic encephalopathy, in whom significant improvements in seizure control were reported. We describe an infant with classical neonatal NKH who presented on the third day of life with hypotonia, poor feeding, respiratory insufficiency resulting in ventilatory support and seizures with burst-suppression pattern on electroencephalogram (EEG). KD initiated at age 6 months for intractable seizures, lead to a dramatic decrease in seizure frequency, EEG improvements, normalisation of plasma glycine levels, reduced spasticity and improved quality of life. KD may be a valuable treatment modality for refractory seizure control in classical NKH.