The aim of this study was to investigate the sedative effects of medetomidine in combination with midazolam or butorphanol for routine imaging procedures in dogs. Eighty client owned dogs were recruited in a prospective, randomised, blinded clinical study and randomly assigned to receive one of four treatments intramuscularly (IM): (1) 30 μg/kg medetomidine (Med30); (2) 20 μg/kg medetomidine combined with 0.3 mg/kg butorphanol (Med20But0.3); (3) 20 μg/kg medetomidine combined with 0.3 mg/kg midazolam (Med20Mid0.3); and (4) 10 μg/kg medetomidine combined with 0.3 mg/kg midazolam (Med10Mid0.3). The level of sedation was evaluated using a composite sedation scale assessed by one investigator (0 = no sedation, 15 = profound sedation). The number of dogs deemed to be adequately clinically sedated and the dose of propofol administered as rescue sedation were recorded. Mean ± standard deviation sedation scores at 30 min after the commencement of treatment in the groups that received Med20But0.3 (9.8 ± 4) and Med20Mid0.3 (8.9 ± 4.4) were not statistically significantly different from each other, but were significantly different from the group receiving Med10Mid0.3 (5.6 ± 3.6). Only Med20But0.3 was significantly associated with adequate clinical sedation, while Med10Mid0.3 was associated with 85% sedation failure. The rescue sedation dose of propofol (1.5 ± 1 mg/kg) for the Med10Mid0.3 group was significantly higher than for other treatments. A sedation score ≥ 10 out of 15 was a satisfactory cut-off to predict adequate clinical sedation. In healthy dogs, the combination of medetomidine with midazolam did not provide comparable sedation to the same dose of medetomidine in combination with butorphanol in a clinical setting.