Purpose: The purpose of this study was to compare the safety of three different sedation regimens for pediatric dental procedures to examine the safety of intranasal dexmedetomidine paired with nitrous oxide (N₂O). Methods: This was a retrospective chart review of 149 three-to six-year-old healthy patients who underwent sedation to complete dental treatment. Forty-nine patients received intranasal dexmedetomidine with nitrous oxide (DEXNO), 47 received oral midazolam with nitrous oxide (MIDNO), and 53 received oral midazolam and oral hydroxyzine with nitrous oxide (MIDHYXNO). Demographic data, procedural times, vital signs, and adverse events were recorded. Results: No patients in any of the three groups experienced major adverse events. All groups experienced some degree of hypotension. One of the 49 DEXNO cases experienced bradycardia intraoperatively. No cases required clinical intervention. Conclusion: This pilot study suggested that intranasal dexmedetomidine with nitrous oxide is a safe sedation regimen for pediatric procedures, comparable to combinations of oral midazolam with nitrous oxide and oral midazolam and oral hydroxyzine with nitrous oxide.