Objectives Rapid, reliable in‐office tests are needed for applying the adopted screen‐and‐treat strategy in Helicobacter pylori‐positive young dyspeptic patients. Design We have evaluated the performance characteristics of a whole‐blood antibody (WBA) test for the detection of H. pylori infection under in‐office conditions. Methods In a prospective double‐blind study, 183 untreated patients referred to a tertiary centre for endoscopy because of dyspepsia were studied. Patients were defined as H. pylori‐positive if two out of three tests (histology, rapid urease test, Gram staining of biopsy smears) were positive, and H. pylori‐negative if all three tests were negative. An in‐office test detecting IgG antibodies to H. pylori (FlexPack HP, Abbott Diagnostics) was used with capillary blood and compared with an ELISA detecting IgG (quantitative) and IgA (qualitative) H. pylori serum antibodies. Results Of the 183 patients, 139 were defined as H. pylori‐positive. The in‐office test had 79% sensitivity, 95% specificity, 98% positive and 59% negative predictive value. The respective values for IgG serum antibodies were 94, 70, 91 and 79% and those for IgA antibodies were 86, 82, 94 and 64%. About 50% of the false‐negative in‐office tests had a serum IgG antibody titre > 100 units. Co‐evaluation of our data with published reports suggested that both the median sensitivity and negative predictive value of the kit are significantly inferior when performed with whole‐blood (five studies) compared with serum (nine studies) (82 versus 92% and 82 versus 93% respectively, P< 0.035). Conclusions Improvement of the performance characteristics of FlexPack HP in‐office test is needed. However, the test may be a useful tool for identifying H. pylori‐positive patients in younger age groups who could be managed without upper gastrointestinal endoscopy. Eur J Gastroenterol Hepatol 12:727‐731