Lamotrigine has been well-studied in patients with bipolar I disorder. This naturalistic open-label study investigated whether long-term adjunctive usage of lamotrigine is effective in patients with bipolar II depression. In this 52-week prospective follow-up study, lamotrigine was added to mood stabilizers in 109 depressed patients with bipolar II disorder. Based on the prospective mood chart, the Clinical Global Impressions-Bipolar Version (CGI-BP)scores were extracted to monitor the changes in illness severity. In addition, time to lamotrigine discontinuation was calculated with the Kaplan-Meier estimate. Depression severity measured by the mean CGI-BP depression score significantly differed between baseline and week 52 and the magnitude of treatment effect was large. The Kaplan-Meier estimate revealed that approximately half of subjects were receiving adjunctive lamotrigine at 52 weeks. In responder analysis, a number of prior hospitalizations for depression and a history of attempted suicide were positively associated with the risk of poor response to lamotrigine treatment. Treatment-emergent adverse events led to 9 cases of lamotrigine discontinuation. In this study, sustained improvement of depression were observed in lamotrigine-treated patients with bipolar II depression. In addition, adjunctive lamotrigine use also appears to be safe and well-tolerated.Adjunctive usage of lamotrigine can be considered as one of the possible option for patients with bipolar II depression supoptimally responsive to prior treatment with conventional mood stabilizers or atypical antipsychotics.