B-type natriuretic peptide (BNP) is a hormone released from cardiac ventricles during episodes of hemodynamic overload. Low density lipoprotein (LDL) apheresis, a procedure for patients with familial hypercholesterolemia (FH) and coronary artery disease (CAD), lowers plasma cholesterol and immediately reduces blood viscosity and coronary vascular resistance while improving myocardial blood flow and microvascular perfusion. Previous studies have demonstrated the ability of LDL apheresis to reduce BNP chronically. We undertook this study to evaluate the difference in reduction of BNP levels following a single treatment with two dissimilar LDL apheresis devices. We conducted a prospective trial involving 27 patients (19 F; age = 59 ± 9 years) with FH who received at least 6 months of bi-weekly LDL apheresis therapy with either the Secura heparin extracorporeal LDL precipitation (HELP) system (N = 17 patients, B. Braun, Inc., Melsungen, Germany) or the Liposorber LA-15 dextran sulfate absorber (DSA) system (N = 10 patients, Kaneka, Inc., Osaka, Japan). We measured BNP levels immediately before and after one treatment of LDL apheresis. Following LDL apheresis, BNP levels were reduced by an average of 40 ± 17% (P < 0.001). Despite treating equal amounts of plasma, the HELP system reduced BNP (45 ± 18%) significantly more than the DSA system (31 ± 11%, P = 0.031). In conclusion, LDL apheresis therapy, possibly through its immediate improvement of vascular flow and/or removal of the peptide from plasma, results in a significant reduction of BNP levels. The increased reduction of BNP by HELP may result from its superior acute alterations of rheological markers.