Pre-anesthetic drugs used for sedation have several effects on the cardiovascular system. Even in minor procedures, they may cause significant cardiac depression and hemodynamic instability. The present study evaluated the effects of medetomidine, or dexmedetomidine, combined with acepromazine and atropine with and without methadone on dogs' sedation scores and cardiovascular system. Forty stray dogs were randomly divided into four groups of ten. Each dog was intramuscularly given one of the compounds of acepromazine (0.05 mg/kg) + dexmedetomidine (5 μg/kg) + atropine (0.03 mg/kg) (Group A); acepromazine + dexmedetomidine + atropine + methadone (0.5 mg/kg) (Group B); acepromazine + medetomidine (10 μg/kg) + atropine (Group C) and acepromazine + medetomidine + atropine + methadone (Group D). Sedation scores, heart rate, respiratory rate, blood pressure, and body temperature were evaluated and recorded at baseline, 5 and 20 minutes after the drug injection. Electrocardiograms (ECG) were also taken at predetermined intervals. The sedation scores in group A were significantly higher at 5 minutes than the baseline. In groups B, C, and D, the sedation scores were significantly higher at 5 and 20 minutes than the baseline. There was no significant difference in the sedation scores during evaluation times between the groups. Heart rate was decreased in all groups after injection. R wave height was increased in all groups. Bradycardia, sinus arrest, and 1st and 2nd-degree heart block were observed in all groups. In conclusion, moderate to deep sedation was achieved in all groups. Heart rate was decreased in all groups, although it returned to baseline earlier in the medetomidine-contained treatments. Occurrences of arrhythmias should be considered when these combinations are used.