This study investigated the induction of anesthesia in swine by injection of tiletamine/zolazepam and ketamine in combination with either dexmedetomidine (TKD) or xylazine (TKX). We hypothesized that TKD would accelerate anesthesia onset and prolong recovery as compared TKX in swine undergoing a noninvasive radiographic procedure. A randomized crossover experiment was performed on 6 healthy, intact, male miniature swine undergoing radiographic examination. Swine were randomly assigned to one of 2 groups: 1) 5mg/kg tiletamine/zolazepam, 2.5mg/kg ketamine, and 0.0125mg/kg dexmedetomidine (TKD) or 2) 5mg/kg tiletamine/zolazepam, 2.5mg/kg ketamine, and 2.5mg/kg xylazine (TKX). Either TKD or TKX was administered intramuscularly at 0.05mL/kg to provide anesthesia for a 45-min radiographic procedure. At 45min after drug administration, atipamezole was administered. During anesthesia, swine were monitored for duration parameters (time to sternal recumbency [onset of anesthesia], lateral recumbency, loss of palpebral reflex, return of the palpebral reflex, and return to sternal recumbency [onset of recovery]) and physiologic parameters (heart rate, %SpO₂, noninvasive blood pressure, and body temperature). Duration and physiologic parameters did not differ between groups at any time point. The results indicate TKD and TKX provide comparable general anesthesia in swine undergoing a radiographic examination.