Background: End stage renal disease (ESRD) is associated with an increase in oxidative stress, cardiovascular disease and cancer. The main treatment for ESRD is haemodialysis (HD), which itself induces repetitive bouts of oxidative stress through membrane biocompatibility and endotoxin challenge. The resulting higher levels of reactive oxygen species in turn produce increased levels of oxidative DNA damage leading to genomic instability which may influence the higher risk of cancer reported in HD patients. Our aims were to measure levels of oxidative DNA damage in HD patients and in age and gender matched control volunteers. Methods: Thirty eight patients receiving HD in the Western Health and Social Services Trust (WHSCT) and 8 healthy volunteers were recruited. Volunteers gave informed consent and non-fasting morning blood samples were taken and assessed for DNA disruption using the comet assay modified to identify oxidative specific damage. Results: The HD patients had significantly elevated levels of alkaline DNA damage (19.46% ± 1.37% vs 3.86% ± 1.36% tail DNA, p < 0.05) and oxidative DNA damage formamidepyrimidine DNA glycosilase (5.81% ± 1.08% vs 1.23% ± 0.43% tail DNA, p < 0.01) and endonuclease III (6.04% ± 1.00% vs 1.98% ± 0.70% tail DNA, p < 0.01) compared to controls, respectively. A positive correlation was observed between the duration on dialysis (months) and levels of Endo III specific damage (p = 0.041). Conclusion: The significant increase in oxidative DNA damage and the positive correlation with duration of HD treatment and Endo III damage may contribute to the increased cancer risk observed in this patient group. Studies are required to investigate the best way to reduce this damage.