question: BACKGROUND: Mechanical power (MP) of artificial ventilation, the energy transferred to the respiratory system, is a chief determinant of adequate oxygenation and decarboxylation. Calculated MP, the product of applied airway pressure and minute ventilation, may serve as an estimate of respiratory muscle workload when switching to spontaneous breathing. The aim of the study was to assess MP's discriminatory performance in predicting successful weaning from prolonged tracheostomy ventilation. METHODS: Prospective, observational study in 130 prolonged mechanically ventilated, tracheotomized patients in a specialized weaning center. Predictive weaning outcome ability of arterial blood gas analyses and indices derived from calculated MP at beginning and end of weaning was determined in terms of area under receiver operating characteristic curve (AUROC) and measures derived from k-fold cross-validation (likelihood ratios, diagnostic odds ratio, F1 score, and Matthews correlation coefficient [MCC]). RESULTS: Forty-four (33.8%) patients experienced weaning failure. Absolute MP showed poor discrimination in predicting outcome; whereas specific MP (MP normalized to dynamic lung-thorax compliance, LTCdyn-MP) had moderate diagnostic accuracy (MCC 0.38; AUROC 0.79, 95%CI [0.71â0.86], p < 0.001), further improved by correction for corresponding mechanical ventilation PaCO2 (termed the power index of the respiratory system [PIrs]: MCC 0.52; AUROC 0.86 [0.79â0.92], p < 0.001). Diagnostic performance of MP indices increased over the course of weaning, with maximum accuracy immediately before completion (LTCdyn-MP: MCC 0.49; AUROC 0.86 [0.78â0.91], p < 0.001; PIrs: MCC 0.68; AUROC 0.92 [0.86â0.96], p < 0.001). CONCLUSIONS: MP normalized to dynamic lung-thorax compliance, a surrogate for applied power per unit of ventilated lung volume, accurately discriminated between low and high risk for weaning failure following prolonged mechanical ventilation.