BACKGROUND: The ratio of dead space to tidal volume (V D /V T) is a clinically relevant parameter in ARDS; it has been shown to predict mortality, and it determines the extent to which extracorporeal CO 2 removal reduces tidal volume (V T) and driving pressure (DP). V D /V T can be estimated with volumetric capnography, but empirical formulas using demographic and physiological information have been proposed to estimate V D /V T without the need of additional equipment. It is unknown whether estimated and measured V D /V T produce similar estimates of the predicted effect of extracorporeal CO 2 removal on DP. METHODS: We performed a secondary analysis of data from a previous clinical trial including subjects with ARDS in whom V D /V T and CO 2 production (_ V CO 2) were measured with volumetric capnography. The estimated ratio of dead space to tidal volume (V D,est /V T) was calculated using standard empiric formulas. Agreement between measured and estimated values was evaluated with Bland-Altman analysis. Agreement between the predicted change in DP with extracorporeal CO 2 removal as computed using the measured ratio of alveolar dead space to tidal volume (V Dalv /V T) or estimated V Dalv /V T (V Dalv,est /V T) was also evaluated. RESULTS: V D,est /V T was higher than measured V D /V T , and agreement between them was low (bias 0.05, limits of agreement-0.21 to 0.31). Differences between measured and estimated _ V CO 2 accounted for 57% of the error in V D,est /V T. The predicted reduction in DP with extracorporeal CO 2 removal computed using V Dalv,est /V T was in reasonable agreement with the expected reduction using V Dalv /V T (bias-0.7 cm H 2 O, limits of agreement-1.87 to 0.47 cm H 2 O). In multivariable regression, measured V D /V T was associated with mortality (odds ratio 1.9, 95% CI 1.2-3.1, P 5 .01), but V D,est /V T was not (odds ratio 1.2, 95% CI 0.8-1.8, P 5 .3