Abstract: In primary hyperoxaluria type 1 (PH 1), deficiency or mis-targeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3–5.7 yr after performing successful PLTx in four children (at the age of 3–9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27–98 mL/min/1.73 m2). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m2) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.