Pharmacological treatment is indicated in children and adolescents with hypertension unresponsive to lifestyle modifications, but there is not enough evidence to recommend 1 class of antihypertensive drugs over others. We performed a network meta-analysis to compare the results of available randomized clinical trials on pharmacological treatment of pediatric hypertension. From a total of 554 potentially relevant studies, 13 randomized placebo-controlled clinical trials enrolling ≥50 patients and a follow-up ≥4 weeks were included. The reduction of systolic blood pressure (SBP) and diastolic BP (DBP) after treatment were the coprimary end points. A total of 2378 pediatric patients, with a median age of 12 years, were included in the analysis. After a median follow-up of 35 days, lisinopril and enalapril were found to be superior to placebo in reducing SBP and DBP, whereas only for DBP, losartan was found to be superior to placebo and lisinopril and enalapril were found to be superior to eplerenone. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were associated with a greater SBP and DBP reduction compared with placebo, likewise the mineralocorticoid receptor antagonist was inferior to angiotensin-converting enzyme inhibitors in DBP reduction. The analysis was adjusted for study-level mean age, percentage of women, mean baseline blood pressure, and mean weight, only the latter significantly affected DBP reduction. According to the present analysis, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers could represent the best choice as antihypertensive treatment for pediatric hypertension. However, because of the paucity of available data for the other classes of antihypertensive drugs, definitive conclusions are not allowed and further randomized controlled trials are warranted.