Direct adsorption of lipoproteins (DALI) from whole blood is the first LDL hemoperfusion technique for extracorporeal LDL and Lp(a) elimination without initial plasma separation. Thus, this technique is characterized by high user-friendliness. In a long-term multicenter study, LDL and lipoprotein (a) (Lp(a)) reductions were 69% and 64%, respectively, per session. Adverse effects were rare, as 95% of the sessions were uneventful. Biocompatibility studies showed only minor blood-adsorber interactions for most parameters; however, there was a significant bradykinin generation. After a single session, significant reductions of plasma viscosity, erythrocyte aggregation and adhesion molecules were documented. A retrospective analysis of 18 chronic DALI patients revealed that in the majority of patients, symptoms like angina and dyspnea as well as their general status and subjective well-being improved significantly. Moreover, the objective cardiovascular event rate (MACE) decreased from a total of 26 in the 3-year period prior to DALI to 6 during a mean follow-up of 3.8 years during chronic DALI therapy. Thus, the average event rate of 0.48 per patient year at baseline could be significantly reduced to 0.09 (P < 0.004) by DALI. This impressive improvement of symptoms and coronary events can hypothetically be related to the improvement of hemorheology and the transformation of unstable into stable plaques by DALI LDL apheresis.