Cytomegalovirus (CMV) infection is frequent after kidney transplantation, typically occurring within the first 100 days post-transplant. This prospective, multicenter study aimed to estimate the frequency of CMV disease beyond 100 days post-transplant and demonstrate the usefulness of virological diagnosis during this period. Of 48 kidney transplant recipients with suspected CMV disease, 17% had positive CMV viremia, and 6% had confirmed CMV disease. The 3 cases of CMV disease presented with high viral loads, viral syndrome associated with tissue-invasive disease. For the 45 patients without confirmed disease, virological diagnosis allowed the identification of other etiologies, mainly infectious or iatrogenic. Although infrequent beyond 100 days, CMV disease can occur and be severe, justifying virological screening in the presence of suggestive signs. Differential diagnosis with other causes remains paramount.