OBJECTIVES: This analysis describes the development, application and comparison of three different equivalence approaches to evaluate equivalence properties of a patient reported outcome (PRO) questionnaire applied to two treatment groups for gastroesophageal reflux disease (GERD). The data used in this analysis was obtained from a medication-monitoring disease registry (iGuard).  Patients using either of the two treatments were randomly invited to complete a measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: Three statistical applications of Confirmatory Factor Analysis (CFA) using a special case of Structural Equation Modelling (SEM) were used to evaluate the equivalence of the TSQM in the two patient populations: 1) equality of the factor scores (measurement equivalence); 2) equality of the variance-covariance matrix (structural equivalence); 3) equality of the measurement error (reliability equivalence). RESULTS: Each statistical test agreed that equivalence had been achieved between the two treatment populations for all the three domains of the TSQM.  The effectiveness and global satisfaction domains exhibited the strongest significant results on all three tests.  However, while the convenience domain exhibited strongly significant equivalence for the measurement equivalence, it only exhibited significant results for the structural and reliability equivalence. CONCLUSIONS: While all three methods indicated the same overall results, there is some suggestion of differing sensitivity amongst the tests.