In light of the established influence of substance use on the onset, course, and outcome of bipolar disorder, we performed a retrospective chart review of patients with bipolar I disorder participating in a randomized controlled trial to further investigate the relationship between alcohol and substance use and first onset of mania. A total of 59.4% (N=101) of the 170 participants were determined to have a history of substance and/or alcohol use. Among the 101 participants with SU, use was coded in 10 (9.9%) as immediately preceding, in 50 (49.5%) as preceding mania, in 7 (6.9%) as following mania, and in 34 (33.7%) as indeterminable. Of the 10 participants with immediately preceding use, 5 experienced their first manic episode immediately after discontinuing a substance. Our findings support earlier reports detailing the high prevalence of substance use among patients with bipolar disorder. Treatments targeting alcohol and substance use among individuals with bipolar disorder are clearly needed, as are prophylactic treatments targeting adolescents and young adults who are at risk for either bipolar disorder or alcohol and substance related disorders.