Primary cleft palate repair may result in significant pain in the immediate postoperative period, which can lead to vigorous crying resulting in wound dehiscence and pulmonary complications. Effective pain control with opioids is the mainstay but administration on the floor has to be countered with the complications associated with their use, chiefly respiratory depression and sedation. We retrospectively examined the efficacies of intraoperative administration of intravenous (IV) dexmedetomidine (DEX) and ketamine (KET) to prevent early postoperative pain in children undergoing primary cleft palate repair and compared the results against relevant literature. The Texas Children's Hospital anesthesia database was queried to identify children undergoing a palatal surgery from December 2011 to December 2012. Inclusion criteria permitted completed primary palatal surgery without major complications and intraoperative administration of DEX or KET. The control group (CTRL) received no additional drug. A comprehensive literature review was performed. A total of 71 pediatric patients underwent palatal surgery during the study period with 46 patients qualifying for analysis. Although results were not significant, consistent trends were observed with regards to lower opioid requirements during the first 24 hours for both medications compared with the CTRL. KET also had shorter time to discharge. The literature review resulted in several studies supporting decreased postoperative pain end points for both DEX and KET. In our sample, DEX and KET reduced postoperative opioid requirements. KET seems to have the added benefit of a shorter hospital stay. These finding are supported in the literature. With further investigation, the addition of these drugs may serve to provide improved pain relief without over sedation in patients undergoing cleft palate repair.