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<b><i>Background:</i></b> The incidence of infective endocarditis (IE) in dialysis patients is higher than the general population. Dialysis patients who develop endocarditis are thought to have a poorer prognosis than other patients with IE. <b><i>Aim:</i></b> To examine the risk profiles, clinical features, and outcomes of patients on dialysis who developed IE in a large cohort. <b><i>Design and Methods:</i></b> A retrospective analysis of all patients developing IE on dialysis (using the modified Duke criteria) was undertaken between 1998 and 2011. Patients were identified from a prospectively collected clinical database. <b><i>Results:</i></b> 42 patients developed IE out of a total incident dialysis population of 1,500 over 13 years. 95% of the patients (40/42) were on long-term haemodialysis (HD) and 5% (2/42) on peritoneal dialysis. Mean patient age was 55.2 years (IQR: 43-69), and mean duration of HD prior to IE was 57.4 months. Primary HD access at the time of diagnosis was an arteriovenous fistula in 35% (14/40), a dual-lumen tunnelled catheter in 55% (22/40), and a dual-lumen non-tunnelled catheter in 10% (4/40). <i>Staphylococcus aureus</i> (including methicillin-resistant<i> S. aureus</i>) was present in 57.1% (24/42). The aortic valve was affected in 42.8% of the patients (18/42), the mitral valve in 30.9% (13/42), and both valves in 9.5% (4/42). 33.3% of the patients had an abnormal valve before the episode of IE. In 21.4% (9/42), valve surgery was performed and mortality was lower in the surgical group compared to the group managed medically during hospitalisation (11.1 vs. 15.2%, p = 0.892), at 3 months (13.1 vs. 19.6%, p = 0.501), and during follow-up (p = 0.207), but this difference did not reach statistical significance. Age >60 years, septic emboli, and methicillin-resistant<i> S. aureus</i> were all adverse prognostic factors. Patients receiving surgery were younger (mean 47.1 ± 14.4 years vs. 57.4 ± 14.3, p = 0.049) and less likely to be infected with <i>S. aureus</i> (surgery 33.3% vs. antibiotics 63.6%, p = 0.046). <b><i>Conclusion:</i></b> This is one of the largest reported series of IE in dialysis patients. The incidence of IE remains high and the prognosis poor in dialysis patients, although patients selected for early valve surgery have good 1-year survival.