OBJECTIVES: Gastroesophageal reflux disease (GERD) is one of the most common chronic disorders of the gastrointestinal tract. The aim of this study was to evaluate the cost of illness in patients affected by GERD visited by general practitioners (GPs). METHODS: A cross-sectional observational multicentre cost of illness study was conducted in the urban area of Milan. Information was obtained through a battery of four questionnaires filled out by 317 GERD patients consecutively enrolled by 47 GPs, investigating clinical (severity and frequency of symptoms), economic (visits, use of drugs, diagnostic tests, hospitalizations, productivity losses), and quality of life (EQ-5D and QOLRAD) variables. We evaluated the costs of the medical resources and the loss of productivity in the perspective of the society. We report on costs and EQ-5D. RESULTS: A total of 317 patients were enrolled, the mean age was 59 years old, and the 58% of the patients were female. The average cost per patient per month was €60.95 and drugs accounted for 65% of total cost. Indirect costs, expressed in terms of days lost at work or inability to do usual activities, were about 0.5 days per patient. Patients who reported chest pain and epigastric pain were more costly compared to those who did not (P = 0.01, Mann-Whitney U test). A strong impairment in the Health Related Quality of Life was also documented: patients reported an average value 64.4 in the 0-100 Visual Analogue Scale of EuroQol (EQ-VAS), significantly lower compared to general population. The EQ-profile indicated that 'pain/disconfort' and 'anxiety/depression' were the most impaired domains. CONCLUSIONS: This is the first Italian study about costs and HRQol of GERD in which patients are enrolled by GPs. The study highlights the relevant economic, social, and quality of life burden of GERD.