As optimal treatment and prognosis differ between asthma and COPD, a new diagnostic approach to differentiating between the two disorders would be clinically desirable. We evaluated the utility of vibration response imaging in differentiating between asthma and COPD. Sixty-six subjects with asthma or COPD were recorded, before and after the administration of a short-acting bronchodilator, using a computerized lung sound analysis device. Gray-scale images of breath sound distribution in the lungs, quantitative data in breath sound graphs (timing, amplitude) and automatic crackle and wheeze detection programs were used to differentiate between asthma and COPD subjects. Imaging data were compared with the clinical diagnosis, made by the standard methods (medical history, physical examination, and spirometric indices). Blinded evaluation of images demonstrated a significantly higher rate of improvement in image dynamics, shape and overall improvement following bronchodilator in subjects with asthma compared with those with COPD. Quantitative data showed distinct patterns in timing and amplitude for these two pathologies. Combined analyses based on qualitative image evaluation and quantitative data demonstrated an overall 85% accuracy (84% for asthma, 86% for COPD) in differentiating between asthma and COPD. Combined qualitative and quantitative evaluations of lung sounds are quite sensitive in distinguishing between lung sound recordings of COPD and asthma individuals. Lung sound features of synchronization in timing and intensity provide objective data that may further differentiate these two airway disorders.