Acutely decompensated heart failure syndrome is a common emergency department presentation in patients with renal failure. B-type natriuretic peptide-mediated vasodilatation may provide a unique bridge in renal failure patients with acutely decompensated heart failure syndrome to treatment with dialysis. We evaluated the efficacy of B-type natriuretic peptide-mediated vasodilatation in acutely decompensated heart failure syndrome emergency department patients with hemodialysis dependent renal failure. This was a prospective, interventional trial. All patients received nesiritide infusion in addition to usual care. Outcome measures included hemodynamic parameters and dyspnea visual analog scale. Eight patients were enrolled, and all demonstrated significant improvement in their dyspnea visual analog scale (Delta 50.1 mm; p < .001 vs. pre-infusion) and APEX score (Delta 48.4%; p < .001 vs. pre-infusion). Three patients improved enough to be discharged from the emergency department for outpatient dialysis. In this hypothesis-generating initial trial, B-type natriuretic peptide-mediated vasodilatation with nesiritide improved symptoms in heart failure patients with hemodialysis-dependent renal failure and appears additive to standard treatment. Further trials are required to test this hypothesis.