The objective of this study was to compare the physiologic and anesthetic effects, and differences, between two intramuscular drug protocols in adult bullsnakes (Pituophis catenifer sayi); the bullsnakes were being anesthetized for a radiotelemetry study. Free-ranging bullsnakes were injected IM with 10 mg/kg butorphanol, followed by either 20 mg/kg alfaxalone or a combination of 0.5 mg/kg midazolam, 0.05 mg/kg dexmedetomidine, and 5 mg/kg ketamine (MDK). After administration, muscle tone, response to stimuli, and jaw tone were evaluated before endotracheal intubation and surgical stimulation to implant coelomic transmitters. If a bullsnake responded to stimulation induced by surgical preparation, or noxious stimuli induced by the surgical procedure, isoflurane was administered to maintain a surgical plane of anesthesia. Heart rate, sedation depth, esophageal temperature, end-tidal CO₂, respirations, time to spontaneous ventilation, extubation, return of righting reflex, and return of spontaneous movement were recorded. Assisted ventilation was initiated if bradypnea (<2 breaths/min) or apnea occurred. Six bullsnakes were evaluated in each group, for a total of 12 bullsnakes. The MDK group was reversed with 0.5 mg/kg atipamezole and 0.02 mg/kg flumazenil IM. All alfaxalone-treated bullsnakes responded to surgical stimulation with movement and required anesthetic maintenance with isoflurane, whereas none of the MDK bullsnakes required inhalant anesthesia. Bullsnakes anesthetized with MDK recovered significantly faster after reversal than bullsnakes in the alfaxalone group. MDK produced a satisfactory level of anesthesia for a minor surgical procedure in bullsnakes, whereas alfaxalone did not. Additional injectable (beyond butorphanol) or inhalant anesthetic agents are recommended for surgical procedures when using alfaxalone.