Clinical observations of mood instability in multiple sclerosis (MS) have led to the hypothesis that bipolar disorder (BD) may be more prevalent in persons with MS than in the general population. This cross-sectional study assesses the prevalence of BD among patients with MS using standardized psychiatric diagnostic interviews and evaluates quality of life. This study demonstrates a higher prevalence of BD in patients with MS compared with the general population. It also reveals the negative impact of BD on quality of life, raises the concern that BD can occur before the onset of neurological symptoms in MS, and suggests that, in some cases, BD may delay diagnosis of MS.