As outlined, multiple competing factors are present when attempting to risk stratify OAC use in patients with ESRD who are undergoing hemodialysis. If we are to extrapolate from the general population, the majority of these patients would receive anticoagulation therapy; but, is extrapolation appropriate? Therapy with statins, BP reduction, and renin-angiotensin system inhibitors have all failed to reduce mortality in the dialysis population despite evidence42–44 of considerable benefit in the general population. Thus, the first step in management involves determining an individual risk-benefit assessment of whether to start OAC (Table 5). Consideration of age, comorbidities, concomitant antiplatelet use, bleeding and stroke history, and the patient's wishes must be weighed carefully. Numerous factors favor the limited use of OAC in this population, such as the high rate of hemorrhagic stokes, the possibility that the majority of ischemic strokes may be lacunar, the high bleeding risk, the shortened lifespan of dialysis patients, and the increased risk of vascular calcification. An approach where OAC for stroke prevention in patients with ESRD and atrial fibrillation who are undergoing hemodialysis should be provided only in those persons who are at high risk for stroke seems reasonable based on the existing literature. Using this approach, OAC then should be offered only to patients who appear to have the highest stroke risk, such as those with a CHADS2 score greater than a modified ORBI score (difference ≥ 2), patient preference, known atrial thrombus, prosthetic heart valves, mitral stenosis, or history of previous thromboembolic stroke. Due to the increased risk of bleeding, patients at low risk such as those who are < 65 years of age, have normal echocardiograms, and are without hypertension, diabetes, or congestive heart failure will likely derive little benefit from OAC. Patients with uncontrolled hypertension, concurrent use of antiphospholipid antibodies, previous severe hemorrhage, a history of treatment noncompliance, frequent falls, calciphylaxis, or severe malnutrition should be considered relatively contraindicated for the use of OAC due to the high risk of subsequent hemorrhage or complications. Although we are cognizant that this approach is controversial, it would appear to be a legitimate approach to treatment as the evidence at this point is limited, and the risk profile appears to be different in the dialysis population.