ABSTRACT: BACKGROUND: Gastroesophageal reflux disease (GERD) is a very common disorder worldwide, comprised of reflux esophagitis (RE) and non-erosive reflux disease (NERD). As more than half of GERD patients are classified into the NERD group, precise evaluation of bothersome epigastric symptoms is essential. Nevertheless, compared with many reports targeting endoscopic reflux esophagitis, large-scale studies focusing on GERD symptoms have been very scarce. METHODS: To elucidate lifestyle factors affecting GERD symptoms, 19,864 healthy adults in Japan were analyzed. Sub-analyses of 371 proton pump inhibitor (PPI) users and 539 histamine H?-receptor antagonist (H?RA) users were also performed. Using the FSSG (Frequency Scale for the Symptoms of GERD) score as a response variable, 25 lifestyle-related factors were univariately evaluated by Student's t-test or Pearson's correlation coefficient, and were further analyzed with multiple linear regression modelling. RESULTS: Average FSSG scores were 4.8 ± 5.2 for total subjects, 9.0 ± 7.3 for PPI users, and 8.2 ± 6.6 for H?RA users. Among the total population, positively correlated factors and standardized coefficients (?) for FSSG scores are inadequate sleep (? = 0.158), digestive drug users (? = 0.0972 for PPI, ? = 0.0903 for H?RA, and ? = 0.104 for others), increased body weight in adulthood (? = 0.081), dinner just before bedtime (? = 0.061), the habit of midnight snack (? = 0.055), lower body mass index (? = 0.054), NSAID users (? = 0.051), female gender (? = 0.048), lack of breakfast (? = 0.045), lack of physical exercise (? = 0.035), younger age (? = 0.033), antihyperglycemic agents non-users (? = 0.026), the habit of quick eating (? = 0.025), alcohol drinking (? = 0.025), history of gastrectomy (? = 0.024), history of cardiovascular disease (? = 0.020), and smoking (? = 0.018). Positively correlated factors for PPI users are female gender (? = 0.198), inadequate sleep (? = 0.150), lack of breakfast (? = 0.146), antihypertensive agent non-users (? = 0.134), and dinner just before bedtime (? = 0.129), whereas those for H?RA users are inadequate sleep (? = 0.248), habit of midnight snack (? = 0.160), anticoagulants non-users (? = 0.106), and antihypertensive agents non-users (? = 0.095). CONCLUSIONS: Among many lifestyle-related factors correlated with GERD symptoms, poor quality of sleep and irregular dietary habits are strong risk factors for high FSSG scores. At present, usual dose of PPI or H?RA in Japan cannot fully relieve GERD symptoms.