Exhaled volatile organic compounds (VOCs) have shown promise in diagnosing chronic obstructive pulmonary disease (COPD) but studies have been limited by small sample size and potential confounders. An investigation was conducted in order to establish whether combinations of VOCs could identify COPD patients from age and BMI matched controls. Breath samples were collected from 119 stable COPD patients and 63 healthy controls. The samples were collected with a portable apparatus, and then assayed by gas chromatography and mass spectroscopy. Machine learning approaches were applied to the data and the automatically generated models were assessed using classification accuracy and receiver operating characteristic (ROC) curves. Cross-validation of the combinations correctly predicted the diagnosis in 79% of COPD patients and 64% of controls and an optimum area under the ROC curve of 0.82 was obtained. Comparison of current and ex smokers within the COPD group showed that smoking status was likely to affect the classification; with correct prediction of smoking status in 85% of COPD subjects. When current smokers were omitted from the analysis, prediction of COPD was similar at 78% but correct prediction of controls was increased to 74%. Applying different analytical methods to the largest group of subjects so far, suggests VOC analysis holds promise for diagnosing COPD but smoking status needs to be balanced.