OBJECTIVE To describe 4 cases of cytomegalovirus (CMV) corneal endotheliitis occurring after Descemet membrane endothelial keratoplasty (DMEK). METHODS This is a retrospective, interventional case series. Case records of 4 patients (one eye each) diagnosed with CMV corneal endotheliitis after DMEK were reviewed retrospectively. Presenting clinical features, treatment, and outcomes were examined. RESULTS Patients' age ranged from 68 to 77 years. Three patients underwent DMEK for failed corneal grafts and 1 for pseudophakic bullous keratopathy. Time from DMEK to presentation ranged from 5 to 15 weeks. Presenting features included corneal edema, pigmented keratic precipitates, mild anterior chamber inflammation, and raised intraocular pressure. Two cases were initially misdiagnosed as graft rejection and treated with corticosteroids. Both worsened, and delayed diagnoses of CMV corneal endotheliitis were made. The two other cases were diagnosed correctly at initial presentation. All cases were confirmed by anterior chamber paracentesis and polymerase chain reaction testing for CMV. All cases were treated initially with topical ganciclovir gel and oral valganciclovir. Three cases showed clinical resolution. Final corrected visual acuity ranged from 20/25 to 20/40. One case failed to respond to topical ganciclovir gel, oral valganciclovir, and intravenous ganciclovir and foscarnet. This patient declined further systemic treatment and was maintained on topical ganciclovir only but subsequently showed spontaneous resolution 3 months later. CONCLUSIONS CMV corneal endotheliitis may occur after DMEK and can closely mimic graft rejection. Polymerase chain reaction testing of aqueous humor is advised for suspect cases. A high index of suspicion is important for prompt diagnosis and initiation of appropriate antiviral treatment.