Background: Cigarette smoking causes accelerated facial wrinkling and predisposes to chronic obstructive pulmonary disease (COPD). However, it has long been recognised that there is a subgroup of susceptible smokers who are at increased risk of developing airflow obstruction. We have tested the hypothesis that there is a common susceptibility for the development of COPD and facial wrinkling in cigarette smokers. Methods: One hundred forty-nine current and ex-smokers were recruited from a family based study of COPD genetics, 68 (45.6%) of whom fulfilled the definition of COPD. One hundred twenty-four (83.2%) had no or minor facial wrinkling (Daniell < IV) and twenty-five (16.8%) were wrinkled (Daniell score >/= IV). Generalised estimating equations were used to adjust for familial correlations between related individuals and the potential confounding effects of age and pack years smoked. Results: The FEV1 was significantly lower in those with wrinkles than in those without (mean difference in FEV1 % predicted -13.7%, 95% CI -27.5 to 0.0, p=0.05) and facial wrinkling was associated with a substantially increased risk of COPD (adjusted OR 5.0, 1.3 to 18.5, p<0.02). The Daniell score correlated with the extent of emphysema on CT scan (p<0.05) and facial wrinkling was also associated with a greater risk of more extensive emphysema (adjusted OR 3.0, 0.1 to 9.3, p=0.05). Conclusion: These data show that facial wrinkling is associated with COPD in smokers and that both disease processes may share a common susceptibility. Therefore facial wrinkling in smokers may be a biomarker of susceptibility to COPD.