Background: Bipolar disorder (BD) is characterized by the alternating occurrence of (hypo)manic and depressive episodes. The aim of the current study was to determine whether personality traits independently predicted the subsequent development of (hypo)manic episodes within a group of patients who were initially diagnosed with depressive and anxiety disorders. Methods: The Netherlands Study of Depression and Anxiety is a cohort study with measurements taken at baseline and at 2-, 4-, 6-, and 9-year follow-up. Development of a (hypo)manic episode during follow-up was assessed with the Composite International Diagnostic Interview and (hypo)manic symptoms were evaluated with the Mood Disorder Questionnaire. The Big Five personality traits were the independent variables in multivariable Cox regression analyses. Results: There were 31 incident cases of (hypo)manic episodes (n = 1888, mean age 42.5 years, 68.3% women), and 233 incident cases of (hypo)manic symptoms (n = 1319, mean age 43.1, 71.9% women). In multivariable analyses, low agreeableness was independently associated with an increased risk of developing a (hypo)manic episode, with a hazard ratio (HR) of 0.54 (p = 0.002, 95% CI [0.37, 0.78]). This finding was consistent with the development of (hypo)manic symptoms (HR 0.77, p = 0.001, 95% CI [0.66, 0.89]). Limitations: The 2-year lag-time analysis reduced the number of participants at risk of a (hypo)manic episode. Conclusions: We conclude that low agreeableness is a personality-related risk factor for incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders. Increased attention to personality deviances could help to recognize BD at an early stage.