Objective: Despite increased risk, most offspring of parents with bipolar disorder (BP) do not manifest BP. The identification of risk factors for BP among offspring could improve preventive and treatment strategies. We examined this topic in the Pittsburgh Bipolar Offspring Study (BIOS). Method: Subjects included 388 offspring, ages 7-17 years, of 233 parents with BP-I or BP-II (via the Structured Clinical Interview for DSM-IV). Offspring diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Present and Lifetime version (KSADS-PL). Analyses focused on the 41 offspring who were diagnosed with BP-I (N = 9), BP-II (N = 5), or BP-NOS (N = 27). Results: Offspring with BP had proband parents who were significantly younger at the time of their birth, were more likely to be female, and had lower socio-economic status, versus proband parents of offspring without BP. Parental clinical variables and obstetric variables were not significantly associated with BP among offspring. History of physical and/or sexual abuse, exposure to antidepressants, and exposure to stimulants was significantly greater among offspring with versus without BP. There was significantly greater prevalence of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, oppositional defiant disorder/conduct disorder (ODD/CD), and exposure to stimulants and antidepressants among offspring with versus without BP. Variables significantly associated with BP among offspring in regression analyses were as follows: older offspring age, younger parent age at birth, offspring anxiety disorders and ODD/CD, and biological coparent with BP. Conclusion: History of anxiety and/or disruptive behavior disorders, as well as presence of bi-lineal parental BP, is associated with elevated risk of bipolar spectrum disorders among offspring. If replicated prospectively, these findings could have implications for the diagnosis and treatment of psychopathology among BP offspring. (Contains 3 tables.)