© 2008 American Medical Association. All rights reserved. Objective: To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an ω-3 fatty acid, improves the motor features of Huntington disease. Design: Six-monthmulticenter,randomized,double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Setting: Forty-one research sites in the United States and Canada. Patients: Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Interventions: Random assignment to placebo or ethyl- EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Main Outcome Measures: Six-month change in the Total Motor Score 4 component of the Unified Huntington’s Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenineguanine repeat length expansions (< 45). Results: At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Conclusion: Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebocontrolled evaluation.