Objective: The objective of this study is to analyze the role of tidal volume (Vt) and positive end-expiratory pressure on the oxygenation ratio (OR) (Pao(2)/Fio(2)) during mechanical ventilation (MV) in children with a normal pulmonary gas exchange on admission. Methods: A retrospective cohort study of children with an admission OR greater than 300 mm Hg and duration of MV greater than 48 hours (n = 96) was done. We analyzed Vt, Fio(2), Pao(2), and positive end-expiratory pressure and calculated Vt (mL/kg) and Pao(2)/Fio(2) based on the measured Vt and weight. Patients were divided into group 1, Vt less than 9 mL/kg (n = 24); 2, Vt 9 to 12 mL/kg (n = 58); and 3, Vt 12 mL/kg or higher (n = 14). Results: Baseline characteristics and OR were comparable. Forty-one percent of patients developed OR less than 300 mm Hg. The proportion of patients developing an OR less than 300 mm Hg was lowest in group 1 and highest in group 3, and differences became more pronounced with longer MV duration: 56%, 58%, and 89% on day 5; 29%, 65%, and 100% on day 7 (P = .05); 0%, 40%, and 100% on day 10 (P = .03). In patients maintaining an OR greater than 300 turn Hg during 10 days of MV, Vt was 9.3 +/- 1.0 vs 12.7 +/- 4.8 mL/kg in patients developing an OR less than 300 mm Hg (P = .05). Mechanical ventilation duration was longer in children developing OR less than 300 mm Hg (P < .01). Positive end-expiratory pressure levels were not significantly different between groups. Conclusion: In ventilated children, Vt was greater than 9 mL/kg were associated with increased development of an OR less than 300 mm Hg and longer duration of MV. (C) 2009 Elsevier Inc. All rights reserved.