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Abstract Background Overuse of proton pump inhibitors (PPIs) – frequently used for relieving symptoms of gastroesophageal reflux disease (GORD) – raises long-term safety concerns, warranting evidence-based non-drug interventions. We conducted a systematic review to evaluate the effect of head-of-bed elevation on relieving symptoms of GORD in adults. Methods We included controlled trials comparing the effect of head-of-bed elevation interventions to control in adults with GORD. Two independent reviewers screened articles, extracted data, and assessed quality of included studies. Primary outcomes were changes in GORD symptoms and use of PPIs. Results We screened 1206 records; and included five trials (four cross-over and one factorial) comprising 228 patients. All five included trials were judged to be at high-risk of performance bias and four of selection bias. Of five included trials, two used ‘bed blocks’ under the bed legs; one used ‘sleeping on a wedge’ pillow, and two used both. High heterogeneity in outcome measures and reported outcomes data precluded meta-analyses. The four studies that reported on GORD symptoms found an improvement among participants in the head-of-bed elevation; a high-quality crossover trial showed a clinical important reduction in symptom scores at 6 weeks (risk ratio of 2.1; 95% CI 1.2 to 3.6). These results are supported by the observed improvement in physiological intra-oesophageal pH measurements. Conclusions Methodological and reporting limitations in available literature preclude definitive recommendations. However, head-of-bed elevation could be still considered as a cheap and safe alternative to drug interventions with unfavourable safety profiles. Protocol registration Open Science Framework: http://osf.io/2hz3j