The purpose of this study was to review the outcome of dialysis-dependent patients undergoing cardiac surgery. We retrospectively reviewed 81 dialysis-dependent patients with a mean age of 62.5 ± 9.4 years who underwent cardiac operations. Mean EuroScore was 7.1 ± 3.9 (>9 in 18 patients). Surgery included coronary artery bypass grafting (CABG) in 43 patients (53.1%), valve surgery in 16 (19.7%), combined CABG plus valve surgery in 19 (23.5%) and major aortic surgery in three patients. In-hospital mortality rate was 13.6%. Most of the deaths occurred in patients who underwent valve procedures or combined surgery. Preoperative New York Heart Association class IV, previous acute myocardial infarction, combined surgical procedures, major aortic surgery, age >70 years, history of heart failure, female gender, the duration of dialysis ≥5 years and urgent/emergent surgery were associated with high relative risk for perioperative death. The actuarial survival was 72.2% at 5 years. Predictors of increased late mortality were heart failure, urgent/emergent surgery, the complexity of the surgical procedures (valve surgery, combined CABG + valve and major aortic surgery) and postoperative low cardiac output syndrome. In dialysis-dependent patients, CABG has an acceptable risk. Results in patients affected by valve lesions associated or not with coronary artery disease are improved by an early referral to surgery, before the onset of symptoms of heart failure.