OBJECTIVES: Assess the construct validity of the GERD-SMQ in relation to esophagitis grade severity, symptom severity, and quality of life within a clinical trial. METHODS: The GERD-SMQ was administered to 1722 subjects participating in a multicenter, randomized double-blind clinical trial. Subjects had a history of erosive esophagitis based on an endoscopy (EGD) performed at study entry or a previous EGD within five years. The Modified Hetzel-Dent Grading Scale was used to determine esophagitis grade scores. A 4-point Likert scale was used to assess GERD symptoms and the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) distress domain assessed quality of life (QOL). Logistic regression, using the GERD-SMQ score (based on previous validation using the heartburn + regurgitation + medication subscores) as the independent variable, was performed to test the GERD-SMQ's degree of association with esophagitis grade and GERD symptoms. ANOVA techniques, using QOL as the independent variable, were employed to test the GERD-SMQ's degree of association with QOL scores. RESULTS: Results of ordinal logistic regression univariate analyses using esophagitis grade score as the dependent variable showed that as GERD-SMQ score increased by one unit, the odds of having more severe symptoms also increased significantly (OR 1.04, p <0.05). Using screening symptoms scores as the dependent variable, the odds of having more severe symptoms significantly increased with observed increases in GERD-SMQ scores (OR 1.22, p <0.0001). Analysis of variance results showed that for every one unit increase in the GSAS distress score, the GERD-SMQ score significantly increased by a factor of 2.39 (p <0.0001). CONCLUSIONS: Significant relationships exist between the GERD-SMQ score, specific symptoms and clinical severity markers demonstrating that the GERD-SMQ is valuable in the clinical trial setting. Further evaluation of the GERD-SMQ is warranted to determine the use of this questionnaire in patients with symptoms of GERD with or without erosive esophagitis.