PRES is a neuro-clinical and radiological syndrome that can result as a consequence of several different conditions including hypertension, fluid overload, and immunosuppressive treatment. Herein, we report two children who received kidney and combined liver–kidney transplantation as treatment for renal hypodysplasia associated with bilateral vesico-ureteral reflux and methylmalonic acidemia, respectively. Early after surgery (seven and 10 days), both patients presented with hypertension and seizures. The patients' immunosuppressive regimen included steroid and calcineurin inhibitors (tacrolimus and cyclosporine, respectively) and basiliximab and one with anti-IL2 receptor. In both cases, the imaging strongly supported the diagnosis of PRES. In details, the CT scan showed hypodensities in the posterior areas of the brain, and brain MRI demonstrated parieto-occipital alterations indicative of vasogenic edema. Treatment with calcineurin inhibitors was temporally discontinued and restarted at lower dosage; arterial hypertension was treated with Ca-channel blockers. Both children fully recovered without any neurological sequels. In conclusion, in children undergoing solid organ transplantation, who develop neurological symptoms PRES, should be carefully considered in the differential diagnosis and once the diagnosis is ruled in, we recommend strict arterial blood pressure control and adjustment or withholding of calcineurin inhibitor therapy should be considered based upon blood levels.