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Background: Siblings of individuals with premature coronary heart disease have a high prevalence of low-density lipoprotein cholesterol (LDL-C) levels requiring treatment., Objective: To evaluate management strategies for high LDL-C levels in apparently healthy 30- to 59-year-old siblings of individuals with documented coronary heart disease prior to age 60 years., Methods: In a 2-year trial of care provided by either a nurse trained in lipid management (NURS) or enhanced primary care (EPC), in which physicians received recommendations based on national guidelines, 156 siblings with LDL-C levels of 4.14 mmol/L (160 mg/dL) were randomized by family. The LDL-C goal levels below 3.36 mmol/L (130 mg/dL) were compared between and within intervention groups. Multiple logistic regression analyses were applied to predict 2-year achievement of the goal., Results: The NURS group achieved a significantly greater percentage of goal LDL-C levels than the EPC group (26% vs 10%; P=.008). The NURS LDL-C levels decreased an average of 0.91 mmol/L (35 mg/dL) while EPC levels decreased by 0.52 mmol/L (24 mg/dL) (P=.09). In the final multivariate model, siblings taking lipid-lowering drug treatment were 6.02 times more likely (95% confidence interval, 2.24-16.18) than those not receiving pharmacotherapy to achieve LDL-C goals; nurse management (P=.09) was marginally significant. Pharmacotherapy was instituted in 45.2% of NURS and 16.7% of EPC siblings (P=.001)., Conclusions: High LDL-C levels in siblings were more effectively treated by a trained nurse, probably related to greater adherence to the application of national guidelines. Nonetheless, the majority of siblings with high LDL-C levels did not meet goal levels 2 years after an index case coronary heart disease event.