The aim of this study was to determine whether CNIs can be safely withdrawn in paediatric patients with declining renal allograft function receiving MMF and corticosteroids for long-term immunosuppression following renal transplantation. We performed a retrospective review of paediatric renal transplant recipients who received MMF with corticosteroids at least three months after transplantation with or without CNI in a single centre. Thirty-eight children (71% male), mean age 7.2 +/- 3.7 yr received MMF and corticosteroids, with 29 (76%) receiving a CNI. Mean follow-up was 59.2 +/- 42 months post-MMF commencement and 109 +/- 98.8 months post-transplantation. Patient and renal allograft survival were 100% and 94%, respectively. There was a significant improvement in eGFR after MMF introduction both in children on a CNI and those where the CNI was withdrawn, with stabilisation of eGFR after two yr. There was no significant difference in the number of acute rejection episodes prior to or following introduction of MMF between the groups. MMF in combination with corticosteroids is a safe and effective immunosuppressive regimen in paediatric renal transplantation. Complete withdrawal of CNIs after conversion to MMF should be considered in all patients, to preserve renal function as evidenced by improved eGFR.