Oesophageal adenocarcinoma (OAC) is more common in men. Androgens may therefore contribute to the pathogenesis of OAC. Prostate cancer (PC), an androgen sensitive tumor with a long natural history, may allow insights into this putative association. West Midlands Cancer Intelligence Unit data from 1977 to 2004 were examined to identify patients with a first malignant primary of PC. Patients were followed until diagnosis of a second primary cancer, death or end of the time period. Age- and period-adjusted standardized incidence ratios (SIR) were calculated as an estimate of the relative risk of a second malignant primary of the oesophagus. Between 1977 and 2004, 44,819 men within the West Midlands developed PC as a first primary malignancy. After exclusion for lack of follow-up, 38,627 men were eligible, providing 143,526 person years at risk for analysis. 86 second primary oesophageal cancers were observed, compared with 110 expected, resulting in an SIR of 0.78 (95% CI 0.62-0.96). There was a reduced risk of OAC 0.7 (0.5-0.95) but not of oesophageal squamous cell carcinoma (OSCC) 1.03 (0.69-1.47). The risk of developing OAC, but not OSCC, is lower than expected in patients with PC. A diagnosis of PC may be associated with aetiological factors that are negatively associated with OAC, or anti-androgen therapy may influence the development of OAC.