Despite the high prevalence of upper gastrointestinal symptoms and associated costs of diagnosis and management, evidence regarding long-term outcomes is scant. We studied symptom outcomes 18 months (FU1) and 8/9 years (FU2) post-index endoscopy to identify demographic, diagnostic and treatment factors associated with outcomes. A retrospective review of medical records at two Australian teaching hospitals identified a cohort of 302 patients who had an index endoscopy (performed by 23 endoscopists) 18 months previously. Patients were interviewed at FU1 and FU2. In total 34% (95%CI: 29.0 - 39.8) of patients were asymptomatic at FU1 and 41% (95%CI: 35.6 - 46.6) at FU2. For 63%, outcomes at FU1 predicted long-term outcome, with 19% (95%CI: 14.6 - 23.4) asymptomatic and 44% (95%CI: 38.4 - 50.0) symptomatic at both times. Those whose symptom status changed were as likely to deteriorate as improve (p > 0.05). Number and severity of presenting symptoms (F = 3.3, df = 3,277, p < 0.05) and older age (F = 2.8, df = 2,301, p < 0.05) were associated with poorer outcomes. Long-term outcome was unrelated to endoscopic diagnosis. Those symptomatic were significantly more likely to be on proton pump inhibitors (PPIs) or Histamine2 Receptor Antagonists (H2RAs) than those who were asymptomatic. Use of PPIs at FU2 was associated with a significantly better outcome than use of H2RAs. However this impact was relatively small, with 69% of patients on PPIs and 84% on H2RAs symptomatic at FU2. Upper gastrointestinal symptoms prompting endoscopy are chronic for the majority of patients regardless of diagnosis. Endoscopic diagnosis is of limited value in predicting long-term outcomes. The association between poor outcome and use of H2RAs and PPIs challenges views about their long-term effectiveness in symptom control.