As the relationship between tobacco smoking and acne remains unclear, we examined the relationship between cigarette smoking and severe acne in a large cohort of young men. Trained nurses interviewed subjects upon discharge from compulsory military service, regarding family history, habits, and tobacco smoking habits. Data was correlated with severe acne status, as diagnosed and coded by board-certified dermatologists. In total, 27,083 male subjects participated in the study from 1983 to 2003, of which 237 (0.88%) had severe acne, 11,718 (43.27%) were active smokers, and 15,365 (56.73%) were nonsmokers at the time of interviews. Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) (P = 0.0078). An inverse dose-dependent relationship between severe acne prevalence and daily cigarette consumption became significant from 21 cigarettes a day (chi2 and trend test: P < 0.0001), odds ratio: 0.2 (95% CI: 0.06-0.63). The study did not aim to establish a temporal correlation, and passive smoking and acne treatments were not measured. Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.