Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited.