Graft versus host disease (GvHD) after liver transplantation has an incidence of 0.1-1%. It is an infrequent but severe and mostly lethal complication. Approximately, 80 cases have been reported in literature so far. A single center experience is reported retrospectively. We performed a retrospective analysis of 1815 liver transplants in our center, transplanted over a period of 17 years. Five patients (5/1815 = 0.28%) with histologically diagnosed GvHD were included in the analysis. Onset of GvHD was between postoperative day (POD) 20 and 60. All patients developed skin rash, being the first symptom in four cases; one patient had joint pain as initial symptom. Macrochimerism was confirmed in all patients. Treatment consisted of augmentation of baseline immunosuppression (n = 4), methylprednisolone (n = 4), and T-cell depleting antibodies (n = 3). One patient received no specific therapy because of her deleterious condition. All patients died because of either haemorrhage or uncontrollable infections. In our experience, GvHD has been an extremely rare, albeit deleterious clinical condition, which was resistant to classical immunosuppressive rescue regimens.