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Background: The diagnosis of hypertension and hypertension-induced target organ injury by the 2022 American Heart Association (AHA) ambulatory blood pressure threshold as compared with 2014 AHA and 2016 European Society of Hypertension (ESH) thresholds has not been evaluated. Methods: In a cross-sectional study (n = 291, aged 5–18 years, at a tertiary care outpatient clinic), we compared 2022 AHA with 2014 AHA and ESH thresholds (revised with 2018 adult ESH thresholds where applicable) to diagnose ambulatory hypertension (AH), and detect ambulatory arterial stiffness index (AASI) and left ventricular target organ injury (LVTOI). Results: The 2022 AHA threshold diagnosed significantly more AH (53%) than the 2014 AHA (42%, p < 0.01) and ESH (36%, p < 0.001) thresholds. The 2022 AHA threshold demonstrated only a moderate agreement with the 2014 AHA (kappa (k) = 0.77) and ESH (k = 0.66) thresholds to diagnose AH. Adjusted logistic regression analysis found that only the 2022 AHA threshold predicted elevated AASI significantly (odds ratio 2.40, 95% CI 1.09, 5.25, p = 0.02; AUC 0.61, p < 0.01). In those with elevated AASI, more participants had AH by the 2022 AHA threshold (72%) than the 2014 AHA (46%, p = 0.02) and ESH (48%, p = 0.03) thresholds. AH defined by the 2022 AHA threshold continued to maintain higher odds, larger AUC, and higher sensitivity to identify LVTOI than the 2014 AHA and ESH thresholds; however, the difference did not reach a statistically significant level. Conclusions: AH defined by the 2022 AHA threshold diagnoses more children with hypertension and identifies more children with hypertension-induced target organ injury than the 2014 AHA and ESH thresholds. [ABSTRACT FROM AUTHOR]