Objective: To assess the clinical effectiveness and cost-effectiveness of low-density-lipoprotein (LDL) apheresis for treatment of patients with homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). Methods: Seven case series and one retrospective review with heparin-induced extracorporeal LDL precipitation (HELP) for the treatment of refractory HMZ and HTZ FH published between January 1998 and May 2007 were included in the analysis. Results: The mean acute decrease in LDL-C ranged from 53-77% with HELP. The mean chronic decrease in LDL-C ranged from 9-46% and the increase in HDL-C ranged from 12-27%. The LDL:HDL ratio exceeded target values. There was a beneficial impact on coronary outcomes demonstrated by a decrease in Agatston scores and a regression in atherosclerotic lesions. Adverse events, ranging 2.9-5.1%, were typically mild and related to vascular access problems. Studies were generally of low quality however performing controlled studies is not feasible given that HELP represents a last therapeutic option for these patients. The annual budget impact was $1.0 and $61.0 million (CAD) for HMZ and HTZ FH patients respectively. Costs were halved with biweekly treatment. The cost per CHD death avoided comparing HELP with Plasma Exchange (PE), current treatment, and with no intervention in HTZ FH was estimated to be $37.5 million and $18.7 million for weekly and biweekly treatment respectively. Although HELP costs twice as much as PE, it avoided 12 deaths versus PE and 22 deaths versus no intervention over a 10-year period. Conclusion: There is evidence of overall clinical benefit of LDL apheresis for HMZ and HTZ FH. The diffusion of LDL apheresis for refractory HTZ FH should factor affordability and potential capital and human resource constraints.