Research suggests that cannabis use affects negatively on onset and outcome of schizophrenia, but less is known about possible effects in mood disorders. Bipolar in- and outpatients (N = 3459) were enrolled in an observational study. The influence of cannabis exposure on clinical and social treatment outcome measures was examined over the course of 1 year, as well as the effects on these associations of third mediating variables. Over 12 months of treatment, cannabis users exhibited less compliance and higher levels of overall illness severity, mania, and psychosis compared with nonusers. Additionally, cannabis users experienced less satisfaction with life and had a lower probability of having a relationship compared with nonusers. There was little evidence that cannabis-outcome associations were mediated by third variables. An independent impact of cannabis use on psychopathologic outcomes in patients with bipolar disorder was apparent, whereas the impact on social outcomes was modest.