General anesthesia poses risks for larger zoo species, like cardiorespiratory depression, myopathy, and hyperthermia. In ruminants, ruminal bloat and regurgitation of rumen contents with potential aspiration pneumonia are added risks. Thus, the use of sedation to perform minor procedures is justified in zoo animals. A combination of detomidine and butorphanol has been routinely used in domestic animals. This drug combination, administered by remote intramuscular injection, can also be applied for standing sedation in a range of zoo animals, allowing a number of minor procedures. The combination was successfully administered in five species of nondomesticated equids (Przewalski horse [Equus ferus przewalskii; n = 1], onager [Equus hemionus onager; n = 4], kiang [Equus kiang; n = 3], Grevy's zebra [Equus grevyi; n = 4], and Somali wild ass [Equus africanus somaliensis; n = 7]), with a mean dose range of 0.10–0.17 mg/kg detomidine and 0.07–0.13 mg/kg butorphanol; the white (Ceratotherium simum simum; n = 12) and greater one-horned rhinoceros (Rhinoceros unicornis; n = 4), with a mean dose of 0.015 mg/kg of both detomidine and butorphanol; and Asiatic elephant bulls (Elephas maximus; n = 2), with a mean dose of 0.018 mg/kg of both detomidine and butorphanol. In addition, the combination was successfully used for standing sedation in six species of artiodactylids: giraffe (Giraffa camelopardalis reticulata; n = 3), western bongo (Tragelaphus eurycerus eurycerus; n = 2), wisent (Bison bonasus; n = 5), yak (Bos grunniens; n = 1), water buffalo (Bubalus bubalis; n = 4) and Bactrian camel (Camelus bactrianus; n = 5). The mean dose range for artiodactylid species except bongo was 0.04–0.06 mg/kg detomidine and 0.03–0.06 mg/kg butorphanol. The dose in bongo, 0.15–0.20 mg/kg detomidine and 0.13–0.15 mg/kg butorphanol, was considerably higher. Times to first effect, approach, and recovery after antidote were short. The use of detomidine and butorphanol has been demonstrated to be a reliable, safe alternative to general anesthesia for a number of large ungulate species.