Adenovirus causes significant morbidity and mortality in solid organ and hematological transplant recipients. Treatment of adenovirus infections includes supportive care, reduction of immune suppression, and in patients with severe disease, intravenous cidofovir. Brincidofovir (CMX001) is a lipid conjugate of cidofovir, with good oral bioavailability, no associated nephrotoxicity, and higher intracellular levels of the active drug compared to cidofovir. We describe a case of severe adenoviral pneumonia in an adult renal transplant recipient who was successfully treated with oral brincidofovir after developing renal insufficiency with intravenous cidofovir. Brincidofovir (CMX001) along with other supportive therapy, may offer an efficacious, safe, and well-tolerated treatment for severe adenoviral infections in solid organ transplant recipients.