Abstract: Direct adsorption of lipoproteins (DALI) is the first low density lipoprotein (LDL)-apheresis technology by which atherogenic LDL and lipoprotein(a) (Lp(a)) can be selectively removed from whole blood without plasma separation. The present follow-up was carried out to evaluate the clinical efficacy, selectivity and safety of long-term DALI apheresis. The follow-up was carried out in an open, prospective uncontrolled multicenter clinical design. Included were 158 drug-resistant hypercholesterolemic patients from 28 apheresis centers. These patients underwent 12 291 DALI sessions between January 1997 and March 2002. The patients suffered from severe atherosclerosis and their mean LDL-C was 188 mg/dL before the sessions. Mean follow-up was 25 ± 16 (range 1–56) months during which 78 ± 53 sessions were carried out. In most treatments, DALI 750 (63%) or DALI 1000 (30%) adsorbers were used. On average, 7423 ± 1495 mL blood was processed at a flow rate of 84 ± 16 mL/min in 102 ± 25 min. Acute reductions by the single DALI sessions averaged 69 ± 12% for LDL-C, 41 ± 18% for TG, 15 ± 10% for HDL-C, 19 ± 11% for fibrinogen and 62 ± 24% for Lp(a) (in patients with Lp(a) > 30 mg/dL). Adverse events were recorded in only 3.9% of the sessions. In this 5-year follow-up, long-term therapy with DALI was safe, effective and selective as LDL-C and Lp(a) could be reduced by >60% per session in approximately 100 min treatment time while HDL-C decrease and the incidence of AE were low.