OBJECTIVE To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a reversal agent. METHODS 11 healthy 2.5-month-old castrated male Landrace mixed-breed pigs. METHODS In a randomized, blinded crossover study design, pigs received the following anesthetic combinations, IM: TZDB (tiletamine-zolazepam [3 mg/kg {1.36 mg/lb}], detomidine [0.18 mg/kg {0.08 mg/lb}], and butorphanol [0.12 mg/kg {0.05 mg/lb}]); TZXB (tiletamine-zolazepam [4 mg/kg {1.8 mg/lb}], xylazine [4 mg/kg], and butorphanol [0.2 mg/kg {0.09 mg/lb}]); and KDB (ketamine [8 mg/kg {3.63 mg/lb}], detomidine [0.18 mg/kg], and butorphanol [0.3 mg/kg {0.14 mg/lb}]). A 7-day washout period was provided between treatments. At 45 minutes of anesthesia, pigs received tolazoline (2 mg/kg [0.9 mg/lb], IM; n = 6) treatment or control (5) treatment with saline (0.9% NaCl) solution. RESULTS All anesthetic combinations induced anesthesia. Endotracheal intubation was completed within 5 minutes after anesthetic administration in all pigs, except in 2 pigs following administration of KDB. Durations (mean ± SD) of endotracheal intubation and lateral recumbency in pigs that did not receive tolazoline were 55.3 ± 4.8 minutes, 83.8 ± 15.8 minutes, and 28.2 ± 4.5 minutes and 112.4 ± 18.7 minutes, 117.2 ± 16.7 minutes, and 79.7 ± 6.0 minutes, respectively, for the TZDB, TZXB, and KDB anesthetic treatments. Tolazoline significantly shortened the duration of anesthetic recovery for all anesthetic treatments without affecting the recovery quality. CONCLUSIONS All 3 anesthetic combinations were suitable for providing anesthesia in pigs. Tolazoline administration shortened the duration of anesthetic recovery without affecting the quality of recovery.