Objectives: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder. Method: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with bipolar II disorder, two with bipolar disorder not otherwise specified) were treated with one of three antidepressants as an adjunct to mood stabilizers. The patients’ switch rates were assessed. Switch was defined as a Young Mania Rating Scale (YMRS) score >13 or a Clinical Global Impression (CGI) mania score ≥3 (mildly ill). Results: Depressed subjects with bipolar II disorder had a significantly lower acute switch rate into hypomania/mania when either YMRS or CGI criteria were used to define switch. Conclusions: These data suggest that depressed patients with bipolar II disorder are less vulnerable than those with bipolar I disorder to switch into hypomania/mania when treated with an antidepressant adjunctive to a mood stabilizer.