The efficacy of a single oral dose of 30 mg/kg of oxfendazole against Fasciola hepatica was evaluated in a controlled study in naturally infected sheep. Sheep were diagnosed by stool microscopy after sedimentation, and positive animals were randomized to oxfendazole (N= 20) or no treatment (N= 20).Anew stool exam was performed 10 days after treatment. All stool microscopies were performed masked to the treatment group. No side effects were noticed. All sheep in the control group remained infected with similar counts of eggs per gram of stools. None of the animals in the treatment group showed Fasciola eggs in stools after 10 days of treatment. A single dose of oxfendazole is highly effective against F. hepatica, providing a new drug alternative for the control of fascioliasis or integrated zoonosis control. Copyright © 2012 by The American Society of Tropical Medicine and Hygiene.