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Context. Prairie dogs (Cynomys spp.) are rodents enjoyed by some humans; yet, they cause crop and property damage, and carry zoonotic disease. Non-lethal control of prairie dogs is of interest in urban/suburban settings. The injectable immunocontraceptive vaccine GonaCon (active ingredient is gonadotropin-releasing hormone [GnRH]) has been shown to be effective at reducing fertility in equine and deer, and is a US EPA-registered vaccine for use in these ungulate species. Aims. To conduct a replicated field study to test efficacy of GonaCon in black-tailed prairie dogs(C. ludovicianus), and if found to be efficacious, to help facilitate the EPA registration of this product for prairie dog management in urban/suburban areas. Methods. Prairie dogs were live-trapped in October–December 2018 in three treatment and three controlsites. Every captured female ≥660 g wasinjected with 0.4 mL of either GonaCon (0.032% w/w GnRH) at treatment sites or a sham vaccine (absent of GnRH) at control sites. Juveniles and adults were counted at all six sites to establish juvenile:adult (ratio) and juvenile density in May–June 2019 (determining initial GonaCon effectiveness) and 2020 (determining persistence of contraception). Key results. In 2019, the juvenile:adult ratio was significantly reduced (P = 0.0022) in GonaCon (mean ± s.e.: 0.23 ± 0.01) relative to the sham (1.10 ± 0.58) sites. Juvenile density was three times greater in sham than GonaCon sites. In 2020, GonaCon sites produced equal offspring to nearby sham sites. Conclusions. GonaCon is highly effective during the first year(2019) but not in the second year(2020) if only a small area (0.6–2.8 ha) orsmall proportion of females in a colony is treated, such as was undertaken in this study. Implications. In 2022, GonaCon− Prairie Dogs was EPA-registered. Treating whole colonies of prairie dogs at once is favoured; yet, if small or partial colony treatment is desired, then annual GonaCon treatment may be needed. [ABSTRACT FROM AUTHOR]