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Background: There is a need for a bedside functional residual capacity (FRC) measurement method that performs well in intensive care patients during many modes of ventilation including controlled, assisted, spontaneous, and mixed. We developed a modified multiple breath nitrogen washout method for FRC measurement that relies on end-tidal gas fractions and alveolar tidal volume measurements as inputs but does not require the traditional measurements of volume of nitrogen or oxygen. Using end-tidal measurements, not volume, reduces errors from signal synchronization. This study was designed to assess the accuracy, precision, and repeatability of the proposed FRC system in subjects with variable ventilation patterns including some spontaneous effort., Methods: The accuracy and precision of measurements were assessed by comparing the novel N₂ washout FRC values to the gold standard, body plethysmography, in 20 spontaneously breathing volunteers. Repeatability was assessed by comparing subsequent measurements in 20 intensive care patients whose lungs were under controlled and assisted mechanical ventilation., Results: Compared with body plethysmography, the accuracy (mean bias) of the novel method was -0.004 litre and precision [1 standard deviation (sd)] was 0.209 litre [mean (sd)] [-0.1 (5.9)% of body plethysmography]. The difference between repeated measurements was 0.009 (0.15) litre [mean (sd)] [0.4 (6.4)%]. The coefficient of repeatability was 0.31 litre (12.7%)., Conclusions: The modified multiple breath nitrogen washout method for FRC measurement provides improved precision and equivalent accuracy and repeatability compared with existing methods during ventilation with variable ventilation patterns. Further study of the novel N₂ washout method is needed.