BACKGROUND: Smoking is a potential risk factor for psoriasis. Both psoriasis and smoking habits are partly explained by genetic factors. However, twin studies investigating the association between these traits are limited. METHODS: Questionnaire-based data on smoking habits and psoriasis were collected for 34,781 twins, aged 20-71 years, from the Danish Twin Registry. A co-twin control analysis was performed on 1700 twin pairs discordant for lifetime history of smoking. Genetic and environmental correlations between smoking and psoriasis were estimated using classical twin modeling. RESULTS: After multivariable adjustment, age group (50-71 vs. 20-49 years) and childhood exposure to environmental tobacco smoke (ETS) were significantly associated with psoriasis in the whole population (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.02-1.29 [P = 0.021] and OR 1.28, 95% CI 1.10-1.49 [P = 0.002], respectively). Risk for psoriasis increased substantially (OR 2.18, 95% CI 1.82-2.61; P < 0.001) for smokers with a history of >5 pack-years, even after adjusting for age, sex, and childhood ETS. Among twin pairs discordant for smoking, risk for psoriasis in the ever-smoking twin was lower among monozygotic twins (OR 1.23, 95% CI 0.59-2.56; P = 0.578) than among same-sex dizygotic twins (OR 2.21, 95% CI 1.36-3.58; P = 0.001). Genetic factors explained 20% (14-25%; P < 0.001) of the correlation between psoriasis and smoking, whereas non-shared environmental factors explained 8% (0-22%; P = 0.504). CONCLUSIONS: Tobacco consumption and childhood ETS are significantly associated with psoriasis. Results indicate shared genetic factors for smoking and psoriasis.