Midodrine hydrochloride is used clinically to treat children with postural tachycardia syndrome (POTS), but it is not effective in all patients. This study was designed to explore the changes in plasma copeptin and its predictive value in assessing the therapeutic efficacy of midodrine hydrochloride in children with POTS. The study included 33 children with POTS and 26 healthy children. The group with POTS received midodrine hydrochloride treatment for 1.5-3 months. The plasma copeptin was measured using a sandwich immunoluminometric assay. A receiver operating characteristic curve was used to explore the predictive value of plasma copeptin. The plasma copeptin in the group with POTS was significantly higher than that of the control group (10.827±2.459 pmol/L vs 8.845±1.471 pmol/L, P<.001). The plasma copeptin in responders to midodrine hydrochloride was significantly higher than that of nonresponders (12.082±1.998 pmol/L vs 9.646±2.301 pmol/L, P=.003). Receiver operating characteristic analysis on the predictive value of plasma copeptin showed that the area under the curve was 0.800 with a 95% CI of 0.640-0.959. Using a plasma copeptin level of 10.482 pmol/L as the cutoff point produced both favorite sensitivity (81.3%) and specificity (76.5%) in predicting the efficacy of midodrine hydrochloride therapy in children with POTS. Plasma copeptin may be considered as a predictive biomarker for the likelihood of successful treatment of children with POTS with midodrine hydrochloride. Copyright © 2014 Elsevier Inc. All rights reserved.