Postural orthostatic tachycardia syndrome (POTS) is common, and has a serious impact on children's quality of life. Midodrine hydrochloride, an α1-adrenoreceptor agonist, is an effective treatment. The study was designed to examine the therapeutic efficacy of midodrine hydrochloride by quantifying changes in blood pressure during the head-up test (HUT), in children with POTS. Overall, 104 out of 110 children with POTS were treated with midodrine hydrochloride and successfully followed-up. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes were analyzed during the HUT. In a retrospective analysis, a receiver operating characteristic (ROC) curve was used to analyze the therapeutic predictive value of pre-treatment changes in SBP, DBP, and a combination of both, from the supine position to standing, in the subjects. The increase of SBP and DBP from the supine position to standing in responders were significantly lower than that of the non-responders. The ROC curve showed that midodrine hydrochloride for children with POTS would be predicted to be effective when the pre-treatment increase of SBP was ≤ 0 mmHg, or when the pre-treatment increase of DBP was ≤ 6.5 mmHg (from the supine position to standing), yielding a sensitivity of 72% and specificity of 88%. The area under the curve was 0.744 and 0.809, respectively. Hence, the results suggested that looking at the changes in blood pressure during the HUT was useful in predicting the response to midodrine hydrochloride in children with POTS.