The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of adenocarcinoma of the oesophagus, and 74 female controls matched by age and general practice. High body mass index (BMI) around the age of 20 years (highest vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI) 1.28-28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR = 0.08, 95% CI 0.01-0.49) were associated with increases in risk. Breastfeeding by women was associated with reduced risk of their subsequently developing this cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20-0.82) and there was a significant dose-response effect with total duration of breastfeeding. The summary population attributable risk from these three factors was 96% (90% if breastfeeding is excluded). We conclude that high BMI in early adulthood and low consumption of fruit are important risk factors for adenocarcinoma of the oesophagus. Breastfeeding may confer a protective effect but this needs confirmation. This cancer is a largely preventable disease in women.