AIM: To investigate the frequency of gastroen-terological diseases in the etiology and the efficacy of proton pump inhibitors (PPIs) in the treatment of cardiac syndrome X (CSX) as a subform of non-cardiac chest pain (NCCP). rnMETHODS: We investigated 114 patients with CSX using symptom questionnaires. A subgroup of these patients were investigated regarding upper gastrointestinal disorders (GIs) and treated with PPI. Patients not willing to participate in investigation and treatment served as control group. rnRESULTS: Thirty-six patients denied any residual symptoms and were not further evaluated. After informed consent in 27 of the remaining 78 patients, we determined the prevalence of disorders of the upper GI tract and quantified the effect of treatment with pantoprazole. We found a high prevalence of gastroenterological pathologies (26/27 patients, 97%) with gastritis, gastroesophageal reflux disease (GERD) and acid reflux as the most common associated disorders. If treated according to the study protocol, these patients showed a significant improvement in the symptom score. Patients treated by primary care physicians, not according to the study protocol had a minor response to treatment (n = 19, -43%), while patients not treated at all (n = 26) had no improvement of symptoms (-0%). rnCONCLUSION: Disorders of the upper GI tract are a frequent origin of CSX in a German population and can be treated with pantoprazole if given for a longer period.