Precooperative children and patients with intellectual disabilities often require intramuscular (IM) sedation prior to the induction of general anesthesia (GA). Ketamine is an effective preinduction sedative but can produce significant adverse side effects. Dexmedetomidine, a sedative with sympatholytic and analgesic properties, may provide advantages when used in combination with ketamine. This retrospective study evaluated the efficacy and safety of IM ketamine with dexmedetomidine for preoperative sedation. We conducted a chart review of all patients (n = 105) treated for dental rehabilitation who received either IM ketamine and dexmedetomidine (study group, n = 74) or IM ketamine and midazolam (control group, n = 31) prior to induction of GA. No significant difference (p = .14) was observed in the time interval from IM administration to operating room entry (median [interquartile range]) between the study and control groups (5 [4–8] vs 5 [2–7] minutes). Patients who received IM dexmedetomidine exhibited significantly lower mean arterial pressures throughout the induction (p = .004) and had lower heart rates (p = .01) throughout the intraoperative period compared with patients who did not receive dexmedetomidine. The combination of dexmedetomidine and ketamine may provide effective and safe IM sedation prior to the induction of GA.