OBJECTIVES:  Alginates are often first line therapy for patients experiencing symptoms of gastro-oesophageal reflux (GORD). Several UK primary care organizations consider alginates to be interchangeable and differentiate products solely on costs; as such many have implemented alginate substitution programs.  The aim of this study was to evaluate the validity of alginate substitution programs by conducting an economic evaluation of the costs and outcomes of the two leading prescribed alginates in the UK.  METHODS:  A decision-analytic model was constructed based on cohort of 3367 patients starting alginate monotherapy in primary care.  Transition probabilities were derived from observed switching patterns during the observation period. The model was populated with previously reported health state utilities to derive quality-adjusted life years (QALYs).  Costs were derived from treatment pathways examining 1st line of therapy / initial therapy, and subsequent therapies (eg, 2nd line, 3rd line, etc). Costs were calculated by summing all lines of treatment prescribed over one year including the costs of clinical consultations. The model calculated incremental cost-effectiveness between GA and Peptac after 2 lines and 5 lines of therapy. RESULTS:  The average annual incremental cost difference between patients starting monotherapy GA and Peptac after 2-lines and 5-lines of therapy was £2.04 and £3.06, respectively.  Disaggregation of costs indicated there was an increased proportion of a cost attributed to consultation visits for those starting on Peptac attributed to higher switching rates requiring a GP consultation.  The incremental cost per quality adjusted life year for 2nd line and 5th line was £2887 and £5305 per QALY.  In the sensitivity analysis the model was insensitive to changes in QoL scores attributed to failing therapy. The cost per QALY figures were moderately influenced by the duration of treatment failure before commencing 2nd line therapy.  CONCLUSIONS:  Based on aggregated costs of therapy and reduced switching rates Gaviscon Advance was cost-effective compared to Peptac.  We suggest that all alginates are clinically not the same and that a broader range of costs and impact on patients should be taken into consideration when implementing therapeutic substitution programs.