The correlation between seroreactivity to Helicobacter pylori-specific antigens and clinical outcomes in gastrointestinal disease remains unresolved. We investigated the anti-H. pylori antibody profile in northeast Thai dyspeptic patients with gastrointestinal disease in order to identify any H. pylori antigens that may be associated with an increased risk of gastrointestinal disease. Eighty-nine H. pylori-infected dyspeptic patients (44 non-ulcer, 23 peptic ulcer, 22 gastric cancer) were included in the study. Patients were considered to have H. pylori infection when at least one invasive method (i.e., culture, rapid urease test, and histology on biopsy specimens) and serological tests including a commercial ELISA (Pyloriset EIA-GIII) and a commercial immunoblot (Helicoblot 2.1; Genelabs Diagnostics), were positive. In addition, the sera of 20 H. pylori-infected blood donors and 10 H. pylori-non-infected blood donors were also randomly collected and analyzed for H. pylori infection by ELISA and Helicoblot 2.1. Immunoreactive protein bands at 116-kDa, 89-kDa, 37-kDa, 35-kDa, 30-kDa, 19.5-kDa, and the current infection marker for H. pylori-infected patients had average frequencies of 97.8%, 77.5%, 36.0%, 25.8%, 79.8%, 58.4%, and 69.7%, respectively. The immunoreactive patterns obtained from the H. pylori-infected patients and H. pylori-infected blood donors were similar. The antibodies to VacA and CagA antigens were not significantly different among the H. pylori-infected gastroduodenal patient groups. The simultaneous presence of antibody to 19.5-kDa antigen and absence of antibody to 35-kDa antigen was associated with an increased risk of gastric cancer (p<0.05). The immunoreactive band to 35-kDa antigen was found at significantly higher levels in peptic ulcer patients, and the 37-kDa antigen was found at significantly higher levels in non-ulcer patients (both p<0.05). Significantly low levels of antibodies to 23-kDa and 85-kDa antigens were found associated with peptic ulcer (p<0.05). We confirm that the universal presence of CagA and VacA in H. pylori-infected patients in Thailand is independent of the gastroduodenal disease. The presence or absence of antibodies to H. pylori-specific antigens may be useful as indirect markers in the screening of H. pylori-infected patients, and may have specific protection roles in H. pylori-related gastroduodenal diseases.