BACKGROUND: Symptoms are essential in the clinical diagnosis of gastro-esophageal reflux disease (GERD). Questionnaires such as GerdQ have been developed as diagnostic aids. GerdQ has been thoroughly validated in well-characterized GERD patients, but has not yet been fully evaluated in a population that includes subjects with atypical symptoms. AIM: To evaluate GerdQ in a population with typical and/or atypical symptoms of GERD, defined by 24-h pH monitoring. The secondary aim was to investigate the outcome of GerdQ depending on the response to proton pump inhibitor (PPI) treatment. METHODS: The study included 646 subjects referred for 24-h pH monitoring due to a clinical suspicion of GERD. All subjects completed GerdQ before performing a 24-h pH monitoring. RESULTS: In total, 377 (58%) subjects were diagnosed with GERD based on symptoms and 24-h pH monitoring (GERD). Of these, 46% had atypical main symptoms. Overall, GerdQ (at cut-off 8) predicted GERD with a sensitivity and specificity of 62% and 74%, respectively. A high specificity but poor sensitivity for diagnosis of GERD was found for atypical main symptoms such as cough, dysphagia and globus. GerdQ had a relatively high sensitivity and specificity in predicting PPI response and a PPV of 99% at cut-off 8. CONCLUSIONS: GerdQ has a diagnostic value in an unselected population presenting with typical and/or atypical symptoms of GERD, but a low sensitivity for diagnosis of GERD was found in subjects with predominant symptoms such as cough, dysphagia and globus.