Objective: The study was designed to examine the effect of selective alpha 1 receptor agonist midodrine hydrochloride in the treatment of children with postural orthostatic tachycardia syndrome. Methods Fifty nine children (23 male, 36 female, age 7-18 yrs, mean age 12.3±2.4 yrs) who came from Peking University First Hospital were included in the study and clinical investigations. They were randomally divided into group I (with midodrine hydrochloride and conventional therapy), group II (with metoprolol and conventional therapy) and group III (with conventional therapy only). Head-up tilt test under quiet circumstance was conducted. At the end of follow-up, the cure rate, improvement rate and effective rate of symptoms were compared among the three groups. Results The cure rate at the end of follow-up in group I was significantly higher than that of group II and group III (60.87% vs 30.00% and 25.00%, P<0.05). The effective rate at the end of follow-up in group I was also significantly higher than that of group II and group III (82.61% vs 50.00% and 43.75%, P<0.05). During follow-up, we discovered that the symptom recurrent rate in group I was significantly lower than group II and group III, respectively (P<0.05), but there was no significant difference between group II and group III. And the time of symptom improvement in group I was shorter than group II and III. Conclusion Selective alpha 1 receptor agonist-midodrine hydrochloride was effective in the treatment of children with postural orthostatic tachycardia syndrome.