Since the clinical benefit of lung recruitment maneuvers (LRMs) is still conflicting, we performed this prospective, randomized, controlled study to investigate whether LRMs should be used in the routine management of acute respiratory distress syndrome (ARDS). This trial was conducted in four intensive care units (ICUs) to compare application of a modified stepwise LRMs with solely lung-protective ventilation in patients with moderate to severe ARDS within 72 h from the onset. The primary outcome was 28-day mortality, and the secondary outcomes were ventilator-free days and ICU-free days. We collected data on 120 ARDS patients from 2009 to 2012, and there was no difference in 28-day mortality between the two groups (28.3% vs. 30.0%, p = 0.84). However, among survivors, patients in the LRM group had a significant longer median duration of ventilator-free days (18 vs. 13 days; p = 0.04) and ICU-free days (16 vs. 11 days; p = 0.03) at 28 days than in the control group. The respiratory system compliance was significantly higher in the LRM group from day 1 to day 7. The occurrence rate of barotrauma was similar in both groups. We concluded that LRMs combined with lung-protective ventilation in early ARDS may improve patient outcomes.[Full article]