Cytomegalovirus (CMV) disease is a common complication following solid organ transplantation with a variety of gastrointestinal (GI) tract manifestations. CMV appendicitis, however, is a rare complication in a solid organ transplant patient, having been reported only once previously. We have recently seen two cases in solid organ transplant recipients at our institution, one a liver recipient and the other a heart recipient. Both patients underwent surgical resection. Pathologic evaluation of both resected appendices as well as polymerase chain reaction (PCR) amplification for CMV from the serum revealed the virus as the etiology. Both patients received induction intravenous ganciclovir followed by oral valganciclovir and have done well post-operatively. Tissue-invasive CMV disease should be considered in the differential diagnosis for solid organ transplant patients with symptoms suggesting acute or chronic appendicitis. Both PCR testing as well as pathologic review of tissue specimens should be considered to ensure accurate diagnosis and management.