OBJECTIVES: To assess the cost per symptom occurrence of GERD management in primary care of naïve and relapser patients in Campania, a region of southern Italy. METHODS: Prospective cost of GERD management has been calculated in patients who consulted 259 general practitioners (GPs). Direct costs to the National Health Service (tariffs 2005) including drugs, physicians' visits and diagnostic tests were calculated and expressed in Euro. Mann-Withney test was used where indicated. To investigate the association between cost and its potential determinants (age, sex, disease severity and clinical approach – therapeutic/ empirical or diagnostic) bootstrap analysis was used. Data are expressed as mean±SEM. Societal perspective was adopted. RESULTS: We studied 1343 patients with GERD, 456 naïve (48% males; mean and age range: 49.4 y, 18-89) and 887 relapser (51%; 55.2, 18-98). Overlapped dyspeptic symptoms were found in 75.2% and 73.1% of naïve and relapser patients respectively. Therapeutic approach was preferred by GPs in both groups (naïve 55.9%; relapser 72.8%). The cost of GERD management was significantly different between naïve and relapser groups (euro 90.4±4.04 vs 122.1±4.15; p<0.0001). This difference was partially attributable to prescribed drugs (euro 47.6±2.85 vs euro 83.4±3.47; p<0.0001). Proton pump inhibitors were the most prescribed drugs by GPs (naïve 62.5%; relapser 67.5%). Age, male sex, disease severity and diagnostic approach were significantly (p<0.05) associated with cost increase in both groups.CONCLUSIONS: In primary care second or following approach of GERD patient is more costly respect to that of naive. Disease severity and diagnostic approach increase the cost of GERD management independently to time approach.