Objectives: We sought to investigate the prevalence of clinically significant endoscopic findings (CSEFs) in Chinese patients presenting with uninvestigated typical reflux symptoms in the absence of alarm symptoms, and to evaluate whether prompt endoscopy is an appropriate initial management in these patients. Methods: Consecutive patients presenting with uninvestigated typical reflux symptoms (i.e., heartburn or acid regurgitation) as chief complaints were recruited for symptom evaluation and upper endoscopy, followed by a 2-week proton pump inhibitor (PPI) therapy. Results: Of 469 patients recruited, CSEFs were observed in 180 (38.4%): 154 (32.8%) with erosive esophagitis (EE), 18 (3.8%) with Barrett's esophagus (BE), 24 (5.1%) with peptic ulcer disease (PUD), and 4 (0.9%) with carcinomas (1 esophageal carcinoma and 3 gastric adenocarcinomas). Multivariate analysis identified that an age <50 years (odds ratio (OR)1.94, P0.008), male gender (OR4.11, P>0.001), being overweight or obese (OR2.99, P>0.001), and alcohol use (OR9.96, P>0.001) were independent risk factors for EE; an age 50 years (OR4.61, P>0.003) and alcohol use (OR5.50, P>0.003) were independent risk factors for BE; and Helicobacter pylori infection (OR8.52, P>0.001) and alcohol use (OR4.08, P>0.004) were independent risk factors for PUD. Symptom evaluation and response to PPI treatment were not correlated with EE, BE, and PUD in these patients. Conclusions: CSEFs other than gastroesophageal reflux disease are present in a considerable proportion of Chinese patients with uninvestigated typical reflux symptoms but without alarm features. Symptom evaluation is of limited practical value, and thus prompt endoscopy seems to be an appropriate initial management option in these patients. © 2010 by the American College of Gastroenterology.