This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings and determined impact on disability days in a nationally representative US sample. A telephone survey of 21,128 adults was conducted including questions about the presence of upper GI symptoms during the past 3 months. Respondents were categorized as symptomatic (ie, reported GI symptoms once per month) or asymptomatic. The survey included questions about missed work, leisure activity, or household activity days. Symptom groupings were identified by using factor analysis, and cluster analysis was used to assign respondents into distinct groups on the basis of these symptom groupings. The prevalence of an average of 1 or more upper GI symptoms during the past 3 months was 44.9%. The most common symptoms experienced during the past 3 months were early satiety, heartburn, and postprandial fullness. Factor analysis identified 4 symptom groupings: (1) heartburn/regurgitation; (2) nausea/vomiting; (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five respondent clusters were identified; the largest clusters were primarily early satiety/fullness (44%) and gastroesophageal reflux disease-like symptoms (28%). Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom profile (4%). Symptomatic respondents reported significantly more missed work, leisure, and household activity days than asymptomatic respondents (all P < .0001). Factor analysis separated GI symptoms into groupings reflecting gastroesophageal reflux disease and dyspepsia: early satiety, postprandial fullness, and loss of appetite; bloating and abdominal pain/discomfort; and nausea and vomiting. These upper GI symptoms were associated with significant loss of work and activity days.