Taenia solium taeniasis/cysticercosis is a zoonotic disease complex in which the pig is an obligate intermediate host. The infection is widespread, particularly in the developing world, and neurocysticercosis is a major cause of human neurologic disease where the parasite is endemic. Despite easy availability, effective anti-parasitic drugs have not been deployed effectively to control disease transmission. We have investigated a vaccine strategy to prevent parasite infection of the pig intermediate host. Such a strategy would interrupt the parasite's life cycle and eliminate the source of infection for humans. Two recombinant antigens selected from the parasite oncosphere life cycle stage were tested in vaccination trials in pigs that were challenged orally with Taenia solium eggs. Both antigens were highly effective in protecting the pigs against infection with the parasite (98.6% and 99.9% protection, respectively). No viable cysts were found in eight pigs vaccinated with one of the antigens. A recombinant subunit vaccine based on oncosphere antigens has the potential to improve the available control measures for T. solium and thereby reduce or eliminate neurocysticercosis.