<i>Background:</i> Symptom-based questionnaires may enhance chronic obstructive pulmonary disease (COPD) screening in primary care. <i>Objectives:</i> We prospectively tested questions to help identify COPD among smokers without prior history of lung disease. <i>Methods:</i> Subjects were recruited via random mailing to primary care practices in Aberdeen, UK, and Denver, Colo., USA. Current and former smokers aged 40 or older with no prior respiratory diagnosis and no respiratory medications in the past year were enrolled. Participants answered questions covering demographics and symptoms and then underwent spirometry with reversibility testing. A study diagnosis of COPD was defined as fixed airway obstruction as measured by postbronchodilator FEV<sub>1</sub>/FVC <0.70. We examined the ability of individual questions in a multivariate framework to correctly discriminate between persons with and without COPD. <i>Results:</i> 818 subjects completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analysis, which was reduced to 17 items for entry into multivariate regression. Eight items had significant relationships with the study diagnosis of COPD, including age, pack-years, body mass index, weather-affected cough, phlegm without a cold, morning phlegm, wheeze frequency, and history of any allergies. Individual items yielded odds ratios ranging from 0.23 to 12. This questionnaire demonstrated a sensitivity of 80.4 and specificity of 72.0. <i>Conclusions:</i> A simple patient self-administered questionnaire can be used to identify patients with a high likelihood of having COPD, for whom spirometric testing is particularly important. Implementation of this questionnaire could enhance the efficiency and diagnostic accuracy of current screening efforts.