The efficacy of injectable doramectin applied at 200 μg/kg was evaluated against adult female Boophilus microplus (Canestrini) (Acari: Ixodidae) in the later stages of engorgement before detachment. Lethal levels of doramectin in the serum of treated cattle (9.7–36.6 ppb) were reached and sustained within 24 h after treatment. However, treatment at 19 or 20 d postinfestation allowed greater tick survival and reproductive capability (IF) than at 18 d postinfestation, indicating that a significant portion of the ticks were able to engorge and detach before obtaining a lethal dose of doramectin. Thus, treatment at 18 d after infestation provided significantly higher overall control (99.5%) than treatment at 19 or 20 d postinfestation (95.8 and 89.1%, respectively). Analysis of control on a daily basis demonstrated that treatment at 18 d postinfestation provided >99% on each day of the evaluation. Conversely, treatment at 19 or 20 d postinfestation produced levels of control ranging from 22.6 to 85.6% during the first 2 d of female detachment, and ≥99% control was not achieved until after the fourth day of female detachment, where it remained throughout the study. Therefore, application of injectable doramectin at ≤18 d after tick infestation was the only treatment regime considered acceptable for use in the U.S. Boophilus Eradication Program. Treatment intervals >18 d postinfestation could pose a substantial risk of dispersing viable ticks to tick-free areas outside the permanent quarantine zone that has been established along the Texas–Mexico border.