Background: Tidal hyperinflation can still occur with mechanical ventilation using low tidal volume (LVT) (6 mL/kg predicted body weight (PBW)) in acute respiratory distress syndrome (ARDS), despite a well-demonstrated reduction in mortality. Methods: Retrospective chart review from August 2012 to October 2014. Inclusion: Age >18years, PaO 2 /FiO 2 <200 with bilateral pulmonary infiltrates, absent heart failure, and ultra-protective mechanical ventilation (UPMV) defined as tidal volume (VT) <6 mL/kg PBW. Exclusion: UPMV use for <24 h. Demographics, admission Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, arterial blood gas, serum bicarbonate, ventilator parameters for pre-, during, and post-UPMV periods including modes, VT, peak inspiratory pressure (PIP), plateau pressure (Pplat), driving pressure, etc. were gathered. We compared lab and ventilator data for pre-, during, and post-UPMV periods. Results: Fifteen patients (male:female ¼ 7:8, age 42.13 AE 11.29 years) satisfied criteria, APACHEII 20.6 AE 7.1, mean days in intensive care unit and hospitalization were 18.5 AE 8.85 and 20.81 AE 9.78 days, 9 (60%) received paralysis and 7 (46.67%) required inotropes. Eleven patients had echocardiogram, 7 (63.64%) demonstrated right ventricular volume or pressure overload. Eleven patients (73.33%) survived. During-UPMV, VT ranged 2-5 mL/kg PBW(3.99 AE 0.73), the arterial partial pressure of carbon dioxide (PaCO 2 ) was higher than pre-UPMV values (84.81 AE 18.95 cmH 2 O vs. 69.16 AE 33.09 cmH 2 O), but pH was comparable and none received extracorporeal carbon dioxide removal (ECCO 2 -R). The positive end-expiratory pressure (14.18 AE 7.56 vs. 12.31 AE 6.84 cmH2O), PIP (38.21 AE 12.89 vs. 32.59 AE 9.88), and mean airway pressures (19.98 AE 7.61 vs. 17.48 AE 6.7 cm H 2 O) were higher during UPMV, but Pplat and PaO 2 /FiO 2 were comparable during-and pre-UPMV. Driving pressure was observed to be higher in those who died than who survived (24.18 AE 12.36 vs. 13.42 AE 3.25). Conclusion: UPMV alone may be a safe alternative option for ARDS patients in centers without ECCO 2 -R.