Abstract This study reports an effective drug combination for the sedation of Priodontes maximus. Three captive adult giant armadilllos were sedated in 2010. The animals were kept at the Municipal Complex, Presidencia Roque Saenz Pena (Chaco, Argentina). A combination of intramuscular anesthetic drugs (butorphanol, xylazine - midazolam) was applied under physical restraint. Isoflurane gas, delivered by facemask, was used for maintenance. The protocol allowed the safe handling of the animals, full physical exams, sample collection, and collection of vital parameters. The protocol was successfully reversed with naltrexone and yohimbine, and the animals recovered uneventfully.