Butorphanol-azaperone-medetomidine (BAM) is commonly used for white-tailed deer (Odocoileus virginianus) immobilization in captive and free-ranging populations. It is a federally regulated controlled substance requiring stringent regulatory compliance, complicating field application. A prescription-only drug combination, nalbuphine-medetomidine-azaperone® (NalMed-A) provides a less-regulated alternative for use by wildlife professionals. Efficacy and safety of these drug combinations for immobilization of deer have not been compared in a controlled trial, and reports of dose-specific effects of NalMed-A on white-tailed deer physiology are lacking. Additionally, residual effects of these drugs on deer behavior, food consumption, and stress response have not been reported. In February through April 2021, we immobilized 30 captive female, adult white-tailed deer in three treatment groups (n=10 each). Hand-injected doses were 1.5 mL BAM intramuscularly (IM; 41.0 mg butorphanol, 13.6 mg azaperone, 16.4 mg medetomidine), 1.5 mL NalMed-A IM (60.0 mg nalbuphine, 15.0 mg medetomidine, 15.0 mg azaperone), and 2.0 mL NalMed-A IM (80.0 mg nalbuphine, 20.0 mg medetomidine, 20.0 mg azaperone). We compared quality of immobilizations and reversals and times to induction and reversal among treatments, collected biological samples to measure stress hormones and blood gases, and conducted observations to determine treatment-related variations in behaviors. When an effective dose was administered, both BAM and NalMed-A produced rapid and smooth immobilization and recovery after reversal. All treatments in combination with manual restraint caused some degree of hyperthermia, hypoxemia, hypercarbia, bradycardia, respiratory and metabolic acidosis, and elevated lactate and serum cortisol. At 60 d, all deer were still alive, with no apparent residual effects. Vital signs of deer exposed to manual restraint and these drug combinations should be monitored closely, with supportive therapy provided when needed. We suggest BAM and NalMed-A are safe for immobilizing deer in situations similar to our trials, although doses may perform differently in deer remotely injected without manual restraint.