Increased body mass index (BMI) confers a survival advantage in maintenance hemodialysis (MHD) patients. Diabetic (diabetes mellitus (DM)) patients undergoing MHD have worse survival. There are limited studies examining the effect of obesity on the risk of death among MHD patients with diabetes. Ninety-eight MHD patients were studied for median follow-up time of 33 months. Patients were classified according to the presence of obesity (BMI ≥ 30 kg/m(2)) or DM. Primary outcome was all-cause mortality. Cox regression was used to evaluate the effect of obesity on time to death. Effect modification and mediation analysis were also performed. Mean age was 49 ± 13 years, 66% were male, 48% were obese and 34% were diabetic. Mortality rates (per 100 person-years) were: 3.4 for non-diabetic obese, 8.6 for non-diabetic non-obese, 14.3 for diabetic non-obese and 18.1 for diabetic obese patients. Log-rank comparing diabetic obese versus non-diabetic obese was significant (p=0.007). Diabetes was associated with an increased risk of mortality after adjustment for potential mediators. Effect modification of obesity in the mortality risk was different between patients with and without diabetes. With adjustment for adipokines, a greater effect modification by diabetes was observed; whereas, adjustment for inflammatory marker did not influence the effect modification. Diabetic obese MHD patients have increased mortality risk compared to non-diabetic obese. Obesity does not offer survival benefits in diabetic obese MHD patients and potentially may have detrimental effects. Larger studies evaluating the effect of adipokines and obesity in outcomes in the diabetic MHD population need to be undertaken.