OBJECTIVES: A high prevalence rate of bipolar disorder (BP) comorbid with alcohol dependence (AD) (BP+AD) in Western patients with BP has been reported, but whether this is true for Han Chinese with BP is uncertain. We explored the prevalence of BP+AD in a Han Chinese population with BP, and investigated the effect of alcohol-metabolizing genotypes on bipolar I disorder (BP-I) + AD and bipolar II disorder (BP-II) + AD. METHODS: Healthy controls (HCs) (n = 672) and 18- to 65-year-old patients with BP (BP-I: n = 530; BP-II: n = 788) were recruited. Patients with any other major or minor mental illnesses, neurological disorders, or organic mental disorders were excluded. A polymerase chain reaction and restriction fragment length polymorphism analysis was used to determine genotypes for alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2), two alcohol-metabolizing enzymes. RESULTS: AD comorbidity rates were 11.7% with BP-I and 17.1% with BP-II. Significantly fewer patients with BP not comorbid with AD (BP-AD) carried the AHD1B*1 allele than did the HCs. Logistic regression analysis showed a main effect of ALDH2*1/*1 only in the BP-I-AD group. In BP+AD patients, logistic regression analysis showed main effects of ALDH2*1/*1 and ADH1B*1/*1 only in the BP-II+AD group. CONCLUSIONS: Having BP-II+AD may be related to ALDH2 and ADH1B, but having BP-I+AD may be related only to ALDH2. We conclude that ALDH2 and ADH1B have different effects in Han Chinese patients with BP-I+AD and BP-II+AD.