Direct HDL-cholesterol (HDLc) assays have several advantages over other assays that are more laborious and time-consuming. A recent College of American Pathologists (CAP) report indicates that at least 385 Beckman LX-20 analyzers use the selective detergent (homogeneous or direct) method for analyzing HDLc. There is no published evaluation of direct HDLc assays on the Beckman platform. Here we report our evaluation of a direct HDLc assay marketed by Beckman for the Beckman LX-20 analyzers. In general, the assay performed well; however, the total error was not within National Cholesterol Education Program (NCEP) guidelines. This was largely because of a significant positive bias that appeared to be due, at least in part, to triglycerides. This bias was worse at HDLc concentrations < 40 mg/dL, which may make it difficult to identify a low HDLc concentration and consequently an increased risk for cardiovascular disease (CVD). © 2004 Wiley-Liss, Inc.