OBJECTIVE To compare sedation in cockatiels (Nymphicus hollandicus) after intranasal administration of midazolam and midazolam-butorphanol. ANIMALS 9 healthy adult cockatiels. PROCEDURES A randomized, controlled, blinded, complete crossover study was conducted. Birds were assigned to 3 treatment groups. Midazolam (3 mg/kg), midazolam-butorphanol (3 mg/kg for each drug), or sterile saline (0.9% NaCl) solution (control treatment) was administered intranasally. Sedation quality was assessed at 3 time points by use of eye and body position; response to visual, auditory, and tactile stimulation; and response during manual restraint on the basis of eye position and struggling intensity. To evaluate attenuation of the manual restraint–induced stress response, heart rate, respiratory rate, and cloacal temperature were measured over a 15-minute period. Treatments were repeated after a minimum washout period of 7 days. RESULTS Median onset of first sedation effects was 85 seconds (range, 60 to 120 seconds) for midazolam and 90 seconds (range, 45 to 180 seconds) for midazolam-butorphanol. Midazolam-butorphanol resulted in significantly less vigorous struggling during restraint than did midazolam or the control treatment. Heart rate did not differ significantly among treatments. The stress-induced increase in respiratory rate was significantly attenuated by midazolam and midazolam-butorphanol, whereas the increase in cloacal temperature was not attenuated by midazolam or midazolam-butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE Intranasal administration of midazolam and midazolam-butorphanol resulted in a rapid onset of sedation in cockatiels. Midazolam-butorphanol resulted in deeper sedation in both restrained and unrestrained birds than did midazolam alone. Midazolam and midazolam-butorphanol both provided safe and effective sedation in cockatiels.