At present, the available methods to diagnose active H. pylori infection are endoscopy with biopsy for histology, culture, rapid urease tests, 13C or 14C urea breath test, urine antibody and the stool antigen test. The aims of this study were to simplify the 13C urea test by measuring 13C in blood rather than breath, and to evaluate the usefulness of the 13C urea blood test for the diagnosis of H. pylori infection. Patients who underwent upper endoscopy for standard clinical indications (e.g. dyspepsia, abdominal pain) were enrolled. A total of 161 patients (93F, 68M, mean age 47±14.2) were evaluated; 50 (31%) of them were H. pylori positive, and 111(69%) were H. pylori negative. H. pylori infection was diagnosed with a rapid urease test (CLO-test) and 13C urea breath test (UBT). Performance characteristics for the 13C urea blood test for diagnosis and evaluation of H. pylori eradication were calculated using UBT and CLO as gold standards. The fifty H. pylori-positive patients were treated with triple antibiotic therapy for two weeks. Four weeks after finishing antibiotic therapy patients were retested with a commercial UBT and urea blood test. The 13C blood test had sensitivities of 92 and 98% and specificities of 96 and 100% as compared with urea breath test and CLO, respectively. We conclude that the 13C urea blood test is highly sensitive and specific for the initial diagnosis and control of eradication of H. pylori infection.