BACKGROUND: Dyspepsia represents a symptom domain rather than a diagnostic condition and covers a wide range of complex, underlying pathophysiologies that are not well understood. The review explores comparative effectiveness interventions for the treatment of symptomatic dyspepsia along a pragmatic-explanatory continuum. The aim is to identify relevant design characteristics applicable to future upper gastrointestinal comparative effectiveness research employing integrative medicine. METHODS: Medline, CINAHL, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and WHO Clinical Trials were systematically searched until January 2019. Included articles were original research with two or more comparative intervention arms for the primary outcome; relief of symptomatic dyspepsia. Evaluation of the studies was conducted using the pragmatic-explanatory continuum indicator summary (PRECIS-2) tool. RESULTS: Thirty-six articles were included in the review. A total of 68 Patient Reported Outcome Measurements (PROMs), utilizing 50 different formats were deployed across the studies. The appraisal process revealed eligibility, flexibility in adherence, flexibility in delivery and organization domains further aligned towards an explanatory design. CONCLUSION: This review identified three design characteristics relevant for future comparative effectiveness research for the treatment of upper gastrointestinal disorders in a community setting. Extensive exclusion eligibility criteria limited the generalization of comparative effectiveness study results by removing sub-groups of the target populations more at risk of dyspeptic symptoms. The requirement for entry endoscopy was found to be common and not always pragmatically justifiable. Development of validated PROMs appropriate for a generic application to upper gastrointestinal disorders would be advantageous for future comparative effectiveness research within integrative medicine.