The objective of this study was to evaluate the effects of tiletamine–zolazepam as a sedative drug in central bearded dragons (Pogona vitticeps) and determine if efficacy differed based on administration route. Ten healthy, adult central bearded dragons received tiletamine–zolazepam (20 mg/kg) either intramuscularly (IM) or subcutaneously (SC) in the cranial body in a randomized, blinded, complete crossover study with a minimum washout period of 2 wk between treatments. Respiratory rate, heart rate, body position, response to restraint, spontaneous movement, righting reflex, and jaw tone were evaluated. All bearded dragons received flumazenil (0.05 mg/kg, SC) in the cranial body 45 min after the initial tiletamine–zolazepam injection. Righting reflex was lost in all bearded dragons receiving tiletamine–zolazepam IM, but only half of the animals lost righting reflex after SC injection. Jaw tone was lost in 90% (9/10) of animals receiving IM injections compared to 40% (4/10) following SC injections. Recovery from sedation was similar between route of administration (IM: 69 ± 39 min, SC: 57 ± 33 min, P= 0.43). Postsedation food intake was suppressed 2 h after return of righting reflex. Based on the findings of this study, IM administration of tiletamine–zolazepam results in a deeper and more consistent plane of sedation in bearded dragons when compared to the SC route. Prolonged recoveries were noted with both routes of administration.