The development and use of safe, effective and practical wildlife contraceptive agents could reduce reproduction in locally overabundant deer populations in situations where traditional management tools such as regulated hunting cannot be employed. GonaCon Immunocontraceptive Vaccine (the commercial name for a particular gonadotrophin-releasing hormone (GnRH)-based emulsion) was tested in adult female white-tailed deer in a fenced herd near Silver Spring, Maryland, USA. Observations of udder condition were used to identify does that had become pregnant. Necropsy observations, histopathology and serum concentrations of anti-GnRH antibodies, luteinising hormone and progesterone were used to compare health and reproductive status of treated (n = 28) and control (n = 15) deer. After receiving one injection of GonaCon, 88% of treated deer did not become pregnant during the first year and 47% did not become pregnant during the second year after vaccination. No adverse health effects related to vaccination with GonaCon were detected, except for localised injection-site reactions in five (29%) of 17 examined, vaccinated deer. Treatment with GonaCon can be a safe and effective means of inducing temporary infertility in wild white-tailed deer. Ultimately, the management value of GonaCon will be determined by natural-resource professionals who use it as one of many tools to manage deer populations.