Although previous work suggests that juvenile onset bipolar disorder increases risk for substance use disorders and cigarette smoking, the literature on the subject is limited. We evaluated the association of risk for substance use disorders and cigarette smoking with bipolar disorder in adolescents in a case-control study of adolescents with bipolar disorder (n=105, age 13.6+/-2.5 years [mean]; 70% male) and without bipolar disorder ("controls"; n=98, age 13.7+/-2.1 years; 60% male). Rates of substance use and other disorders were assessed with structured interviews (KSADS-E for subjects younger than 18, SCID for 18-year-old subjects). Bipolar disorder was associated with a significant age-adjusted risk for any substance use disorder (hazard ratio[95% confidence interval]=8.68[3.02 25.0], chi(2)=16.06, p<0.001, df=1), alcohol abuse (7.66 [2.20 26.7], chi(2)=10.2, p=0.001, df=1), drug abuse (18.5 [2.46 139.10], chi(2)=8.03, p=0.005, df=1) and dependence (12.1 [1.54 95.50], chi(2)=5.61, p=0.02, df=1), and cigarette smoking (12.3 [2.83 53.69], chi(2)=11.2, p<0.001, df=1), independently of attention deficit/hyperactivity disorder, multiple anxiety, and conduct disorder (CD). The primary predictor of substance use disorders in bipolar youth was older age (BPD-SUD versus BPD+SUD, logistic regression: chi(2)=89.37, p<0.001). Adolescent bipolar disorder is a significant risk factor for substance use disorders and cigarette smoking, independent of psychiatric comorbidity. Clinicians should carefully screen adolescents with bipolar disorder for substance and cigarette use.