The study evaluated seven intensive care unit (ICU) ventilators (Veolar FT, Galileo, Evita 2, Evita 4, Servo 900C, Servo 300, Nellcor Puritan Bennett 7200 Series) with helium-oxygen (HeO2), using a lung model, to develop correction factors for the safe use of HeO2. A 70:28 helium-O2 mixture (heliox) replaced air and combined with O2 (HeO2). Theoretical impact of HeO2 on inspiratory valves and gas mixing was computed. True fraction of inspired oxygen (FIO2del) was compared with fraction of inspired oxygen (FIO2) set on the ventilator (FIO2set). True tidal volume (VTdel) was compared with VT set on the ventilator (VTset) in volume control and with control VTdel at FIO2 1.0 in pressure control. FIO2del minimally exceeded FIO2set (</= 5%) except with the 7200 Series (FIO2del > FIO2set by 125%). In volume control, with the Veolar FT, Galileo, Evita 2, and Servo 900C, VTdel > VTset, with the 7200 Series VTdel < VTset (linear relationship, magnitude of discrepancy inversely related to FIO2set). With the Evita 4, VTdel > VTset (nonlinear relationship), whereas with the Servo 300 VTdel = VTset. In pressure control, VTdel was identical to control measurements, except with the 7200 Series (ventilator malfunction). Correction factors were developed that can be applied to most ventilators.