BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the patient's general health. GERD carries the risk of several adverse outcomes and there is widespread use of potent acid-inhibitors, which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD. METHODS: Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs), and prospective observational studies were included. RESULTS: Weight loss was followed by decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late evening meals increased time with supine acid exposure compared with early meals (5.2% point change), and head-of-the-bed elevation decreased time with supine acid exposure compared with a flat position (from 21% to 15%). CONCLUSIONS: Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head-of-the-bed elevation is effective in nocturnal GERD.