The study aimed to examine the serum serological response among H. pylori-infected patients with various upper gastrointestinal diagnoses; to ascertain whether it could be predictive to the diagnostic outcome of dyspepsia. One hundred seventy H. pylori-infected patients with dyspeptic symptoms but without previous treatment were enrolled, including those with duodenal ulcer disease (N = 47), gastric ulcer (N = 23), nonulcer dyspepsia (N = 60), gastric cancer (N = 34), and MALToma (N = 6). Sera from dyspeptic patients without H. pylori infection (N = 33) were used as controls. During endoscopy, gastric biopsies were taken for CLO-test, histology, and culture for the detection of H. pylori infection, defined by a positive culture or positive results of both CLO-test and histology. Total H. pylori IgG antibody was tested by an ELISA method. Antibody responses to specific H. pylori proteins were tested by a western blotting system. Of patients with H. pylori-infected gastroduodenal diseases, 76.5%, 42.9%, 23.6%, 46.7%, 84.1%, 76.5%, 82.9%, and 32.4% on average, showed responses to the 116-kDa (CagA), 89-kDa (VacA), 60-kDa, 45-kDa, 35-kDa, 30-kDa, 26.5-kDa, and 19.5-kDa H. pylori-specific proteins, respectively. A significant association was found between the serological response to 19.5-kDa and 26.5-kDa proteins and malignant outcome of H. pylori infection (P<0.02). Among patients without malignancy, the absence of a band at 19.5 kDa was statistically associated with the presence of an ulcer (P<0.05). The presence of serum antibody against CagA is not different between patients with ulcer and with malignancy in clinical diagnosis. The serum test for detecting antibodies against lower-molecular-weight proteins of H. pylori, such as those of 19.5 and 26.5 kDa, could be useful to identify H. pylori-infected patients at risk of peptic ulcer or malignancy.