We report a rare case of cytomegalovirus (CMV) colitis presenting radiologically as acute appendicitis in an immunocompetent 71-year-old man known for ulcerative colitis. Although initial imaging revealed acute appendicitis, a lack of clinical improvement with antibiotic therapy prompted further evaluation with colonoscopy, which led to the diagnosis of CMV colitis on a background of mild ulcerative colitis flare. Most individuals infected by CMV will exhibit lifelong latency; however, the virus can reactivate under impaired immune status (eg, transplant recipients, those receiving immunosuppressive therapy). Patients with underlying inflammatory bowel disease are especially at risk of CMV colitis during an acute flare. This case illustrates a unique presentation of CMV colitis in an immunocompetent host, with initial imaging studies revealing acute appendicitis.