It is well known that smoking is a major risk factor for lung disease and respiratory symptoms. We examined the association between smoking and the risk of chronic bronchitis in a large twin sample. In a population-based questionnaire study of 13,649 twins, aged 50-71years, from the Danish Twin Registry, we identified 1,146 twin pairs, discordant for a lifetime history smoking. We performed co-twin control analysis to examine the impact of smoking on the risk of chronic bronchitis. The prevalence of chronic bronchitis was 9.7%. In the total sample, high age, living without a spouse, and smoking remained statistically significant predictors with an up to tenfold increased risk of chronic bronchitis in the heaviest smokers compared with never-smokers, after multivariate adjustment. Among twin pairs discordant for smoking, chronic bronchitis was significantly more common in the smoking twin compared with the nonsmoking co-twin. There was no differential effect of smoking on the risk of chronic bronchitis in monozygotic and dizygotic twins. The risk of chronic bronchitis increases with age and increasing tobacco consumption. The results indicate a direct relationship between smoking and development of chronic bronchitis, but other environmental factors, such as exposure to household smoking in childhood and living without a spouse, also play a role.