The latest data released to the public from the Chinese Ministry of Health reported 120,940 confirmed H1N1 cases and 659 deaths on the Chinese mainland. We performed a prospective, single-center study to investigate the efficacy of lung recruitment maneuver (RM) with high-level positive end-expiratory pressure (PEEP) in patients with the 2009 influenza A (H1N1)-associated acute respiratory distress syndrome (ARDS). Eighty-four patients with H1N1-associated ARDS were admitted to emergency intensive care units between October 2009 and February 2012. During pressure control ventilation, if arterial oxygen saturation (SpO2) is consistently <88% for >30 minutes, an RM with high-level PEEP is performed to normalize lung volume at 30 cmH2O for 60 seconds. The RM was considered initially a responder if SpO2 increased >3% within 15 minutes; otherwise, an SpO2 increase <3% would be considered initially a nonresponder. Variations on oxygen metabolism and hemodynamic parameters were also measured before and after initial RM with high-level PEEP. After the initial RM, 40 patients (47.6%) with influenza-associated ARDS displayed an increase (≥3%) in SpO2 (the responder group), and 44 patients (52.4%) had no significant improvement (<3%) in SpO2 (the nonresponder group). Among 84 patients with influenza-associated ARDS, 56 patients survived and 28 patients died. There was significant difference in mortality rate between the responder group and the nonresponder group (7 out of 40 vs 18 out of 44; P = 0.019). The initial PEEP level in the responder group was lower than that of the nonresponder group (P = 0.028). The initial mean duration of mechanical ventilation in the responder group was also shorter than that of the nonresponder group (P = 0.011). Furthermore, the initial dynamic lung-thorax compliance was obviously higher in the initially responder group than in the nonresponder group (P = 0.038). Initial response of lung RM with high-level PEEP may be associated with good clinical outcome of patients with influenza-associated ARDS. The initial PEEP level, duration of mechanical ventilation, and dynamic lung-thorax compliance dynamic lung-thorax compliance may be potential factors in influencing the initial response to RM.