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Background: Multiple activity monitors are utilized for the estimation of moderate- to vigorous-intensity physical activity in youth. Due to differing methodological approaches, results are not comparable when developing thresholds for the determination of moderate- to vigorous-intensity physical activity. This study aimed to develop and validate count-to-activity thresholds for 1.5, 3, and 6 metabolic equivalents of task in five of the most commonly used activity monitors in adolescent research. Methods: Fifty-two participants (mean age = 16.1 [0.78] years) selected and performed activities of daily living while wearing a COSMED K4b2 and five activity monitors; ActiGraph GT1M, ActiGraph wGT3X-BT, activPAL3 micro, activPAL, and GENEActiv. Receiver-operating-characteristic analysis was used to examine the area under the curve and to define count-to-activity thresholds for the vertical axis (all monitors) and the sum of the vector magnitude (ActiGraph wGT3X-BT and activPAL3 micro) for 15 s (all monitors) and 60 s (ActiGraph monitors) epochs. Results: All developed count-to-activity thresholds demonstrated high levels of sensitivity and specificity. When cross-validated in an independent group (N = 20), high levels of sensitivity and specificity generally remained (≥73.1%, intensity and monitor dependent). Conclusions: This study provides researchers with the opportunity to analyze and cross-compare data from different studies that have not employed the same motion sensors.