BACKGROUND: No studies have evaluated the predictive value of alarm symptoms for organic dyspepsia and organic upper gastrointestinal (GI) diseases based on Rome IV criteria in the Chinese population. AIM: To evaluate the predictive value of alarm symptoms for dyspeptic patients based on Rome IV criteria. METHODS: We performed a cross-sectional study of dyspepsia patients who met the inclusion and exclusion criteria at two academic urban tertiary-care centers from March 2018 to January 2019. Basic demographic data, dyspeptic information, alarm symptoms, lifestyle, examination results, family history and outpatient cost information were collected. Dyspepsia patients with normal findings on upper GI endoscopy, epigastric ultrasound and laboratory examination and without -associated dyspepsia were classified as functional dyspepsia. RESULTS: A total of 381 patients were enrolled in the study, including 266 functional dyspepsia patients and 115 organic dyspepsia patients. There were 24 patients with organic upper GI disease among patients with organic dyspepsia. We found that based on the Rome IV criteria, alarm symptoms were of limited value in differentiating organic dyspepsia and organic upper GI diseases from functional dyspepsia. Age (odds ratio (OR) = 1.056, = 0.012), smoking (OR = 4.714, = 0.006) and anemia (OR = 88.270, < 0.001) were independent predictors for organic upper GI diseases. For the comparison of epigastric pain syndrome, postprandial distress syndrome and epigastric pain syndrome combined with postprandial distress syndrome, the results showed that there were statistically significant differences in anorexia ( = 0.021) and previous visits ( = 0.012). The ClinicalTrials.gov number is NCT03479528. CONCLUSION: Most alarm symptoms had poor predictive value for organic dyspepsia and organic upper GI diseases based on Rome IV criteria. Gastroscopic screening should not be based solely on alarm symptoms.