RATIONALE: Mechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MP(ratio)). OBJECTIVE: To define a threshold value of MP(ratio) leading to the development of VILI. METHODS: In a population of 82 healthy pigs, a threshold of MP(ratio) for VILI, as assessed by histological variables and confirmed by using unsupervised cluster analysis was 4.5. The population was divided into two groups with MP(ratio) above or below the threshold. MEASUREMENTS AND MAIN RESULTS: We measured physiological variables every six hours. At the end of the experiment, we measured lung weight and wet-to-dry ratio to quantify edema. Histological samples were analyzed for alveolar ruptures, inflammation, alveolar edema, atelectasis. An MP(ratio) threshold of 4.5 was associated with worse injury, lung weight, wet-to-dry ratio and fluid balance (all p < 0.001). After 48 h, in the two MP(ratio) clusters (above or below 4.5), respiratory system elastance, mean pulmonary artery pressure and physiological dead space differed by 32%, 36% and 22%, respectively (all p < 0.001), being worse in the high MP(ratio) group. Also, the changes in driving pressure, lung elastance, pulmonary artery occlusion pressure, central venous pressure differed by 17%, 64%, 8%, 25%, respectively (all p < 0.001). LIMITATIONS: The main limitation of this study is its retrospective design. In addition, the computation for the expected MP in pigs is based on arbitrary criteria. Different values of expected MP may change the absolute value of MP ratio but will not change the concept of the existence of an injury threshold. CONCLUSIONS: The concept of MP(ratio) is a physiological and intuitive way to quantify the risk of ventilator-induced lung injury. Our results suggest that a mechanical power ratio > 4.5 MP(ratio) in healthy lungs subjected to 48 h of mechanical ventilation appears to be a threshold for the development of ventilator-induced lung injury, as indicated by the convergence of histological, physiological, and anatomical alterations. In humans and in lungs that are already injured, this threshold is likely to be different.