Purpose Extracorporeal shock wave lithotripsy (ESWL) requires sedation in pediatric patients. Dexmedetomidine is a relatively new agent used for sedation. The aim of this randomized prospective study was to compare the effects of dexmedetomidine–ketamine and midazolam–ketamine combinations on the recovery time, hemodynamic and respiratory variables, and side effects in pediatric patients undergoing ESWL. Methods Fifty pediatric patients aged between 2 and 15 years who were scheduled for elective ESWL were randomized into two groups. In Group D we applied dexmedetomidine at1 μg/kg, given over 10 min, and a bolus of 1 mg/kg ketamine for sedation. In Group M we applied midazolam at a 0.05 mg/kg bolus dose 10 min before the procedure and a 1 mg/kg bolus of ketamine. We measured and monitored the hemodynamic variables, oxygen saturation, and recovery time, and we also monitored the side effects. Results Four patients in group D refused to complete the study; 21 patients in group D and 25 patients in group M completed the study. We found the recovery time eye-opening time (9.3 ± 4.5 vs. 16.2 ± 6.5 min; p  < 0.001), verbal response time (12.8 ± 4.9 vs. 19.2 ± 7.2 min; p  < 0.001), and the cooperation time (17.1 ± 5.0 vs. 23.3 ± 7.7 min; p  < 0.001) to be shorter in the dexmedetomidine group. Also, the heart rate values were lower in the dexmedetomidine group at the 20th minute of the procedure (99.1 ± 19.0 vs. 118.7 ± 7.3 beats/min; p  = 0.016). Conclusion In this study we found the recovery time to be shorter, with hemodynamic stability, in the dexmedetomidine group, compared with the midazolam group. So we can conclude that dexmedetomidine may be a good and safe alternative agent for sedation, with a shorter recovery period than midazolam, in the pediatric population.