To retrospectively compare computed tomographic virtual gastroscopy (VG) and conventional optical gastroendoscopy for the differentiation of malignant and benign gastric ulcers. The institutional review board approved this study and confirmed that informed consent was not required. Gastric ulcers in 115 patients (mean age, 64.7 years; range, 31-86 years; 61 men, 54 women) were evaluated by using endoscopy and VG. Ulcer shape, base, and margin and periulcer folds were evaluated by two independent reviewers. Malignant gastric ulcers were identified by irregular, angulated, or geographic shape; uneven base; irregular or asymmetric edges; and disrupted or moth-eaten appearance of periulcer folds near the crater edge and/or clubbed or fused folds. Benign gastric ulcers were identified by smooth and regular shapes, even bases, clearly demarcated and regular edges, and folds that tapered and converged toward the ulcer. The performance of VG and endoscopy for the diagnosis of benign and malignant gastric ulcers was evaluated by using histopathologic results as the reference standard. The McNemar test was used to compare VG and endoscopic data. A P value less than .05 was considered to indicate a significant difference. At histopathologic examination, 39 gastric ulcers were benign, while 76 were malignant. VG and endoscopy had sensitivities of 92.1% (70 of 76) and 88.2% (67 of 76), respectively, for overall diagnosis of malignant gastric ulcers, and specificities of 91.9% (34 of 37) and 89.5% (34 of 38), respectively, for overall diagnosis of malignant gastric ulcers. Endoscopy was more sensitive in depicting malignancy according to ulcer base (85.5% [65 of 76] vs 68.4% [52 of 76]) (P = .034), and VG was more specific in depicting malignancy according to ulcer margin (78.4% [29 of 37] vs 63.2% [24 of 38]) (P = .034). VG and endoscopy were almost equally useful in distinguishing between malignant and benign gastric ulcers. http://radiology.rsnajnls.org/cgi/content/full/2522081249/DC1.