Abstract: Objective To explore the risk factors and clinical characteristics of non-erosive reflux disease (NERD) based on a prospective single disease database of functional gastrointestinal disease. Methods Using a customized case report form, we collected the personal and clinical data of all study participants in an online database for further analysis. High-resolution manometry and multichannel intraluminal impedance-pH monitoring were performed in some cases. Results A total of 504 NERD cases and 152 control cases were included in our database. The NERD patients consisted of 266 (52.8%) female patients and 238 (47.2%) male patients; 32.7% of the patients were from rural areas and 67.3% from urban areas; 23.1% of the patients worked in the line of business, 19.6% were civil servants, 19.2% were unemployed, and 17.1% were workers; the mean disease duration of the patients was 27.88±16.33 month. Our analysis showed that adverse events in life (P=0.045, OR=1.954), frequent drinking (P=0.040, OR=3.957), snoring (P=0.002, OR=2.334), late meals (P=0.002, OR=2.752), and anxiety or depression (P=0.003, OR=2.723) were all independent risk factors for NERD. Of these patients, 60.81% had varying degrees of ineffective contraction of the esophageal body. The total liquid reflux events differed significantly between NERD patients with hiatal hernia and those without (P<0.05). Conclusion Unhealthy eating habits and lifestyle, history of adverse events, anxiety and depression, snoring, poor esophageal motor function and hiatal hernia are significant factors contributing to NERD, which is related with occupation and living areas and occurs most commonly at 30-50 years of age.