The aim of this study was to determine the prevalence of upper gastrointestinal symptoms (UGIS) in a general population and quantify the relationship of those symptoms to healthcare utilization and quality of life. In-person interviews were conducted with 2056 United States and Canadian residents selected at random. Subjects reported frequency and severity for 11 symptoms, prescription and over-the-counter medication use, primary care and specialty physician visits in prior three months, and completed the Psychological General Well-Being Scale. For analyses, subjects were classified into four mutually exclusive symptom groups: gastroesophageal reflux disease (GERD) -like, GERD plus motility-like (GERD+), ulcerlike, and motility-like. Of the total sample, 51.4% reported the occurrence of at least one UGIS in the prior three months. Subjects in the GERD+ and ulcer groups used more prescription medications and were more likely to see a physician about the symptoms (P<0.001). Subjects with symptoms demonstrated poorer quality of life compared to subjects with no symptoms. The prevalence of UGIS in the general population is high and symptoms are associated with significant health-care utilization and poorer quality of life.