Although chronic obstructive pulmonary disease (COPD) has been considered a disease of Caucasian men, recent data show mortality rising faster among women and African-Americans. Some have suggested these groups are more susceptible to tobacco smoke. We examined this issue in our own population of COPD patients.Beginning in March 2003 we prospectively developed a COPD research database to facilitate recruitment for clinical trials. Enrollees are recruited from clinics and paid advertising and their demographics, medical/smoking histories, and spirometric data are recorded. We examined the smoking histories and pulmonary function of enrollees over 45, with ⩾20 pack-years of smoking, FEV 1 /FVC (forced expiratory volume forced vital capacity) <0.70, and a race-adjusted post-bronchodilator FEV 1 <80%. The primary outcome was the loss of lung function per pack-year smoked, or Susceptibility Index (SI), calculated using the formula: (% predicted FEV 1 −100)/pack-years.A total of 585 patients enrolled during the study period and 330 met our inclusion criteria. Caucasians were older than African-Americans (63 vs. 58, P=0.0003) and had more pack-years of smoking (57 vs. 43, P=0.0003). There were no differences in lung function or bronchodilator reversibility among the racial or gender subgroups. Caucasians had less loss of lung function per pack-year smoked than African-Americans (SI=-1.02% vs. −1.34%, P=0.007) and men less than women (SI=-0.98% vs. −1.21%, P=0.001). Caucasian males appeared relatively protected from tobacco smoke (SI=-0.93%), while African-American women appeared most susceptible (SI=-1.42%).There are important differences in racial and gender susceptibility to tobacco smoke among patients with COPD. African-American females appear to be at highest risk and may benefit most from smoking cessation.