Graft-versus-host disease (GvHD) is a rare but fatal complication after solid organ transplantation arising in 1% to 2% of cases. We report 2 cases of GvHD after orthotopic liver transplantation. Both patients had a history of hepatitis C virus (HCV) infection prior to transplantation. Both cases presented between 1 and 4 months after transplantation with rash, pancytopenia, and/or diarrhea. Our second case also developed oral and ocular manifestations after liver transplantation, which are more commonly described after stem cell transplantation. Diagnosis in both cases was made by clinical presentation in conjunction with histopathology and flow cytometry. Both patients were treated by increasing immunosuppression with tacrolimus and high-dose steroids. Response to treatment differed based on the degree of pancytopenia. Our case report is distinguished by several factors such as the context of GvHD presentation and the role of HCV treatment. Diagnosis of GvHD is difficult and often delayed due to nonspecific presentation that overlaps with other conditions. Furthermore, the relation between HCV treatment and potential initiation of GvHD in solid organ transplant patients is unclear.