People diagnosed with Barrett’s oesophagus are approximately 30-40 times more likely to develop oesophageal adenocarcinoma than the healthy population. Gastro-oesophageal reflux disease and obesity are widely recognized risk factors for oesophageal adenocarcinoma. At present there is a lack of evidenced-based interventions aimed at reducing cancer risk in individuals with Barrett’s oesophagus. This study examined the effect of exercise on adiposity, gastro-oesophageal reflux and obesity-related hormones in overweight and obese males with Barrett’s oesophagus. Inactive males with Barrett’s oesophagus (n=33), aged 18 to 70 years, who were overweight or obese (BMI 25.0 – 34.9 kg/m2) were recruited and randomised to receive either a 24-week, moderate-intensity aerobic and resistance exercise intervention (60 minutes, 5 days/week) or stretching (45 minutes, 5 days/week). Body composition, waist circumference, gastro-oesophageal reflux symptoms and circulating concentrations of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), insulin and glucose were measured at baseline, 12-weeks and 24-weeks. Insulin resistance was determined using HOMA. Intervention effects were analysed using generalised linear models adjusting for baseline values. At 24-weeks (n=32), the exercise group significantly reduced waist circumference (intervention effect -4.5 [95% CI -7.5, -1.4] cm; p < 0.01) and leptin concentration (intervention effect -3.0 [95% CI -6.4, 0.5] ng/mL; p = 0.09) compared to the control group. A non-significant reduction in fat mass was also observed (intervention effect -1.7 [95% CI -4.9, 1.7] kg; p = 0.32). Changes in gastro-oesophageal reflux symptoms, HOMA, IL-6, TNF-α and adiponectin levels did not differ between groups. Insulin, CRP and total adiponectin significantly decreased within both groups (p < 0.05). These data suggest that regular moderate-intensity aerobic and resistance exercise may improve risk profiles associated with cancer risk in inactive, overweight and obese males with Barrett’s oesophagus. Larger trials are required to confirm these findings.