Objectives The aim of this study is to analyse four alternatives for handling gastro-oesophageal reflux (GER) from the pharmacoeconomic standpoint: proton pump inhibitors (PPI), H2-histamine receptor antagonists (H2RA), antacids (AA) and alginates. Methods A cost-effectiveness model based on a decision analysis that represents clinical evolution in a 4-week time horizon has been used, by applying any of the four alternatives for handling GER. Each alternative is evaluated according to its effectiveness: absolute benefit increase is then expressed as a percentage (%). The incremental C-E ratio (ICER) among the treatments has been calculated, as this allows finding out the cost necessary to achieve an extra unit of effectiveness. Costs have been calculated from the patient's perspective ('pocket payments'). Key findings Cost effectiveness for interventions with alginate and AA have been estimated at US$ 957 and US$ 2177 respectively. The ICER between both treatments implies that each unit of difference among the interventions would cost US$ 426. Each extra unit of effectiveness between both treatments in a 100-patient cohort would cost US$ 426. Treatments with AA and alginate prevailed over those with H2RA and PPI respectively. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Conclusions According to the results of this study, the intervention with alginate proved to be more cost effective than AA. Treatments with AA and alginate prevailed over those with H2RA and PPI respectively. Sensitivity analyses evidenced the need for a moderate modification in the values assigned to the variables for offsetting the C-E difference between alginates and AA. © 2012 The Authors. JPHSR © 2012 Royal Pharmaceutical Society.