Background Mechanical ventilation is a critical therapeutic intervention in the management of patients with respiratory failure. Understanding the implications of different ventilation modes is essential in preventing ventilator-induced lung injuries (VILI). Recently, mechanical power has emerged as a critical element in the development of VILI and mortality. Previous bench work studies have suggested that new optimal (adaptive) modes, such as Adaptive Ventilation Mode 2 (AVM-2), can reduce the mechanical power in turn might reduce the rates of VILI. This study aims to compare the conventional Pressure-Controlled Ventilation (PCV) mode with an emerging design of Adaptive Ventilation Mode-2 (AVM-2), to measure the differences in mechanical power, alongside it’s components of PEEP, Tidal, Elastic, Resistive, Inspiratory, Total work, tidal volume, driving pressure and Power Compliance Index. Methods Between January 2023 and June of 2023, we conducted a prospective crossover study on twenty-two subjects admitted to our ICU within the first day after initiation of mechanical ventilation. Subjects were initially started on PCV settings chosen by the primary treatment team, then switched to AVM-2 with comparable minute ventilation. Mechanical power and its work components (tidal, resistive, PEEP, elastic, inspiratory, total), tidal volume, driving pressure, respiratory rate, and positive end-expiratory pressure, were recorded for each patient every 15 min for the duration of 2 consecutive hours on each mode. Statistical analysis, including paired t-tests were performed to assess the significance of differences between the two ventilation modes. The data is provided in means and 土 SD. Results There were significant differences between PCV and AVM-2 in mechanical power (J/min): 21.62 土 7.61 vs 14.21 土 6.41 (P < 0.001), PEEP work (J): 4.83 土 2.71 vs 4.11 土 2.51 (P < 0.001), Tidal work (J): 3.83 土 1.51 vs 2.21 土 0.89 (P < 0.001), Elastic work (J): 8.62 土 3.13 vs 6.32 土 3.21 (P < 0.001), Resistive work (J): 3.23 土 1.61 vs 1.81 土 1.31 (P 0.013), Inspiratory work (J): 6.95 土 2.58 vs 4.05 土 2.01 (P < 0.001), Total work (J): 11.81 土 3.81 vs 8.11 土 4.23 (P < 0.001). There were significant differences between PCV and AVM-2 in tidal volume (ml): 511 土 8.22 vs 413 土 10.21 (P < 0.001), tidal volume / IBW 7.38 土 1.74 vs 6.49 土 1.72 (P 0.004), driving pressure (cmH2O): 24.45 土 6.29 vs 20.11 土 6.59 (P 0.012), minute ventilation (L/min): 8.96 土 1.34 vs 7.42 土 1.41 (P < 0.001). The respiratory rate (bpm) was not significantly different between PCV and AVM-2 19.61 土 4.32 vs 18.32 土 1.43 (P 0.176). There were no significant differences between PCV and AVM-2 in static compliance (ml/cmH2O) 20.24 土 5.16 vs 22.72 土 6.79 (P 0.346), PaCO2 (mmHg) 44.94 土 9.62 vs 44.13 土 10.11 (P 0.825), and PaO2:FiO2 243.54 土 109.85 vs 274.21 土 125.13 (P 0.343), but significantly higher power compliance index in PCV vs AVM-2: 1.11 土 0.41 vs 0.71 土 0.33 (P < 0.001). Conclusion This study demonstrates that the choice of mechanical ventilation mode, whether PCV or AVM-2, significantly impacts mechanical power and its constituent variables. AVM-2 mode was associated with reduced mechanical power, and its’ components alongside the driving pressure, and tidal volumes, indicating its potential superiority in terms of lung-protective ventilation strategies. Clinicians should consider these findings when selecting the most appropriate ventilation mode to minimize the risk of ventilator-associated complications and improve patient outcomes. Further research is warranted to explore the clinical implications of these findings and to refine best practices in mechanical ventilation. Key words: Mechanical power, Work, PCV, AVM-2, VILI