The diffusing capacity of the lung is usually reported as both the diffusing capacity (DLCO) and the diffusing capacity divided by the alveolar volume (DLCO/VA). However, it is unclear which measure to use when interpreting pulmonary gas exchange. We therefore conducted this study to determine whether the DLCO or the DLCO/VA is a better predictor of oxygen desaturation with exercise.We retrospectively analyzed the pulmonary function records of all patients who had measurement of their diffusing capacity and 6-min walk oximetry in our university pulmonary function laboratory over a 2-year period.There were data available on 97 patients, most of who had interstitial lung disease and/or lung volume restriction. The median DLCO was 51% predicted and the median DLCO/VA was 64% predicted. The prevalence of exercise desaturation was 43%. The overall sensitivity and specificity as determined by the area under the receiver operator characteristic (ROC) curve was higher for DLCO than DLCO/VA, with an optimal cut-off of normal of 55% predicted. The positive predictive values were equally low for both measures, ranging from 50% to 70%. After adjustment for VA, there were no differences between the ROC curves or predictive values for DLCO and DLCO/VA.After adjusting for VA, neither the DLCO nor the DLCO/VA was better at predicting oxygen desaturation with exercise. The optimal cut-off of normal was 55% predicted.