OBJECTIVE Familial hypercholesterolemia is a dominantly inherited disorder caused by mutations at the locus for the low-density lipoprotein receptor and is frequently associated with premature coronary artery disease. This study was performed to determine whether arterial grafting was associated with long-term benefits for patients with familial hypercholesterolemia. METHODS During the past 18 years, 101 patients with heterozygous familial hypercholesterolemia underwent primary coronary artery bypass grafting, with one hospital death. Group 1 patients (n = 31) received only saphenous vein grafts. Group 2A patients (n = 47) received one internal thoracic artery graft and supplemental vein grafts, and group 2B patients (n = 23) had multiple arterial grafts. After operation, all patients received diet therapy and intensive cholesterol-lowering drug therapy. Thirteen patients received low-density lipoprotein apheresis. RESULTS During a mean follow-up period of 95 months, 8 patients died, 9 underwent reoperation, and 12 received catheter intervention. The overall survival was 82% (95% confidence limits, 65%-97%) at 18 years after operation. The survival in group 2 was higher than that found in group 1 (P =.01). The overall freedom from major cardiac events (myocardial infarction, cardiac death, reoperation, and catheter intervention) was 57% (95% confidence limits, 40%-74%) at 16 years after operation. The freedom from reoperation in group 2 was higher than that found in group 1 (P =.03). There was no difference in the survival or freedom from major cardiac events between groups 2A and 2B. CONCLUSIONS Arterial grafting improved the long-term freedom from reoperation in patients with familial hypercholesterolemia. Additional benefit of multiple arterial grafting could not be identified.