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Objective The aim of this study was to compare and assess the pain perception, anxiety, and discomfort between two different rapid maxillary expansion (RME) protocols in patients with unilateral cleft lip and palate (UCLP). Design This is a prospective study. Setting The study was done in a comprehensive cleft care center. Patien and Participants The sample included 26 patients between ages 6 and 9 years with a history of repaired UCLP. Interventions The patients were randomly allotted into 2 groups—Group A and Group B. Group A received 1 RME activation per day and Group B received 2 activations per day. The participants after RME activation completed a self-report questionnaire and ranked the pain and anxiety levels using Faces pain scale and Hamilton anxiety scale, respectively. The evaluation was done every day for 1 week. Main Outcome Measure The Faces Pain Scale, Hamilton Anxiety Scale, and self-report questionnaires assessed the pain, anxiety, and discomfort experienced by the patients after 2 different types of RME activation protocols. Results Group B experienced significantly higher pain in the molars than Group A ( P < .001). There was no significant difference between the 2 RME activation protocols regarding anxiety and jaw discomfort. Conclusion Patients who received 2 activations per day experienced significantly higher levels of pain in the molars compared to the patients who received a single activation per day. There were no significant differences between the 2 activation protocols in terms of pain in the palate, tongue, anxiety, and jaw discomfort.