OBJECTIVES: Gastroesophageal reflux disease (GERD) is one of the most common chronic disorders of the gastrointestinal tract. The aim of the study was to evaluate the cost of illness and the Health-Related Quality of Life (HRQoL) in patients with GERD visited by gastroenterologists. METHODS: A cross-sectional observational multicenter cost of illness study was conducted. Patients were enrolled by gastroenterologists of three specialist centers in Italy. Information about demographic characteristics, symptoms (frequency and severity), resource use (visits, drugs, clinical examinations and hospitalizations) and productivity losses was obtained through an ad hoc questionnaire. We evaluated costs of the medical resources and loss of productivity in the perspective of the Italian society. To evaluate the HRQoL we used a battery of two questionnaires (SF-36 and EQ-5D). RESULTS: Ninety-one patients were enrolled, the mean age was 52 years old and the 49% of the patients were males. The average cost per patient-month was € 75.42 and hospitalizations accounted for the 34% of total medical costs. Indirect costs, expressed in terms of lost productivity, were about 0.2 working days lost per patient-month. Presence of chest pain and eructation was associated with higher overall costs (P <0.05). A strong impairment in the HRQoL was also documented: SF-36 showed that ‘role-physical’, ‘bodily pain’ and ‘role-emotional’ were the most impaired dimensions. These results are consistent with those obtained with the EQ-5D profile. Frequency and intensity of symptoms were significantly associated with lower levels of HRQoL. CONCLUSIONS: This is the first study investigating cost of care and HRQoL of patients with GERD in Italy. The study highlights the relevant economic, social, and quality of life burden of GERD.