Introduction: Preliminary investigations suggest that Barrett's esophagus (BE) and esophageal adenocarcinoma (ECA) may have a genetic predisposition. Aim: To determine whether patients with BE or ECA have an increased prevalence of BE and/or ECA in their families. Methods: Patients with BE and ECA were identified through a pathology database at a university hospital. The diagnosis of BE or ECA was reconfirmed by an experienced gastrointestinal pathologist. The control group consisted of a cohort of patients enrolled in a pharmacotherapy study of esophagitis. All control subjects had gastroesophageal reflux symptoms and endoscopic evidence of esophagitis without BE or ECA. Patients and controls were given a standardized questionnaire (modified Mayo GERQ) about severity and duration of reflux symptoms, risk factors, and detailed family history. Prevalence of a family history of BE or ECA was compared between index patients and control subjects. Results: Questionnaires were returned by 18/54 (33%) in the BE/ECA group and 24/46 (52%) in the control group. Four (22%) index patients in the BE/ECA group compared to none (0%) in the control group reported at least one first- or second- degree relative with BE or ECA (p = 0.03, Fischer's exact). One patient reported 2 first-degree relatives (1 ECA and 1 BE), and another reported an identical twin with BE. Compared to the control group, the BE/ECA group tended to be older (mean age, 62 years vs. 55 years, p < 0.1) and had a greater proportion of men (72% vs. 42%, p < 0.1). Race, severity of GERD symptoms, duration of GERD symptoms, smoking history, alcohol history, and obesity (Body Mass Index >30 kg/m2) were not significantly different between the two groups. Conclusions: Patients with Barrett's esophagus or esophageal adenocarcinoma are more likely to have a family history of BE or ECA compared to GERD patients without BE. Prospective studies to determine the prevalence of BE in family members of patients with BE or ECA are needed.