Controlling fertility of feral horses through the use of long-acting contraceptives or sterilization approaches has been championed as a reasonable and humane solution for addressing overpopulation problems in several western states. However, methods to accomplish long-term contraceptive efficacy of horses following a single treatment have been lacking. In fall 2002 and spring 2003, we initiated a study to compare the long-term efficacy of a single-shot contraceptive vaccine directed at gonadotropin releasing hormone (GonaCon™) to that of a single-shot vaccine directed at the zona pellucida (SpayVac) and to the use of intrauterine contraceptive devices (IUD). Both vaccines were administered with AdjuVac™, an adjuvant developed at the National Wildlife Research Center. The objectives of the study were to determine: 1) 3-year efficacy for preventing pregnancy, 2) whether the contraceptive effects are reversible, and 3) whether there are contraindications. The Nevada Department of Agriculture provided the feral mares, which were maintained at the Nevada State Penitentiary, Carson City, facility. Mares were dewormed and given health vaccinations annually. Eight untreated control mares were compared to 12 mares treated with SpayVac, 16 mares treated with GonaCon™, and 15 mares treated with copper-containing IUDs. Only 25% (2/8) of the control mares were not pregnant or infertile in the first year. All mares in the SpayVac group were infertile, and 94% (15/16) were infertile in the GonaCon™ group during the first breeding season. In Year 2, 80% (10/12) of the SpayVac-treated mares and 60% (9/15) of the GonaCon™-treated mares were infertile. In Year 3, 80% of the SpayVac mares and 53% (8/15) of the GonaCon™-treated mares were infertile. For IUD-treated mares, 80% (12/15) were infertile after Year 1, but only 29% (4/14) and 14% (2/14) were infertile after Years 2 and 3, respectively. For IUD mares that were infertile, it was possible to visualize the IUD by ultrasonography, leading us to conclude that mares that became pregnant had lost their IUDs. For mares given SpayVac, uterine edema was commonly observed. In Years 2 and 3, antibody titers for SpayVac were progressively lower compared to titers observed in Year 1.