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Symptoms of gastroesophageal reflux disease (GERD) are the primary risk factor for Barrett's esophagus (BE). However, the significance of age at symptom onset is unknown. We examined the effects of multiple dimensions of GERD exposure on BE risk and whether these associations are modified by other risk factors for BE.Data were from a cross-sectional study of 683 Veterans Affairs patients undergoing an elective esophagogastroduodenoscopy (EGD) or a study EGD concurrently with colonoscopy from primary care clinics. We compared 236 patients with both endoscopically suspected and histologically confirmed BE to 447 primary-care patients (“primary-care controls”) without endoscopically suspected BE on their study EGD. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression.Age at onset <30 years of frequent (at least weekly) GERD symptoms was associated with highest risk of BE (OR=15.1, 95% CI 7.91–28.8), and risk increased linearly with earlier age at onset of symptoms (P-trend=0.001). This association was independent of cumulative GERD symptom duration. People with early onset GERD symptoms who reported ever using proton pump inhibitors were at especially high risk of BE (OR=31.1, 95% CI 13.9–69.7). In people with frequent GERD symptoms, BE risk was almost 80% lower amongHelicobacter pylori-positive patients (OR=2.60, 95% CI 1.26–5.40) than those negative forH. pylori(OR=8.24, 95% CI 5.00–13.6).Risk of BE increased linearly with earlier age at onset of frequent GERD symptoms. Age at symptom onset may help practitioners decide which patients with GERD symptoms to refer for endoscopic screening for BE.