Purpose: The purpose of this article is to analyze the effect of a pressure-regulated volume-controlled ventilation mode on lung mechanics and gas exchange in patients with acute respiratory failure. Materials and Methods: We ventilated 10 patients with two pressure-limited modes: pressure-controlled ventilation (PC) and pressure-regulated volume-controlled ventilation (PRVC) in random order, for 1 hour each. Patients were stabilized on volume-controlled ventilation (VC) for 30 minutes before, between, and at the end of PC and PRVC to reach baseline conditions. At the end of every VC period and at 30 and 60 minutes of PC and PRVC, respiratory mechanics, gasometrics, and hemodynamic parameters were collected. Results: We found no significant differences between the three VC periods. Comparing VC with the two pressure-limited ventilation modes, peak pressure decreased from 29.4 ± 9.1 cm H2O (VC) to 25.9 ± 8.4 (PC 60 minutes) and 26.1 ± 8.2 (PRVC 60 minutes), and PaCO2 decreased significantly from 38.6 ± 3.1 mm Hg (VC) to 36.7 ± 2.8 (PC 60 minutes) and 36.8 ± 2.9 (PRVC 60 minutes). Conclusions: Pressure-limited ventilation allows mechanical ventilation for the same tidal volume as VC but results in a lower peak inspiratory pressure and a slightly lower PaCO2. The mechanism responsible for this gas exchange effect is unknown but is probably related to a better air distribution of the decelerated flow. The clinical relevance of this phenomenon remains to be established.