ObjectiveThe possible presence of gender-related differences in patients with bipolar disorder (BD) may have diagnostic and therapeutic implications. This multicenter study aimed to investigate gender differences in BD in the largest Italian database collected to date, on behalf of the Italian Chapter of the International Society of Bipolar Disorders.MethodsA total of 1674 patients (males: n = 714; females: n = 960) from different psychiatric departments were compared according to gender on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (gender) at the univariate analyses, preliminary multiple logistic regression analyses were performed. A final multivariable logistic regression was then performed, considering gender as the dependent variable and statistically significant demographic/clinical characteristics as independent variables.ResultsThe results of the final multivariable logistic regression analysis with previous statistically significant demographic and clinical variables were the following: female gender was less frequently associated with employment (odds ratio [OR] = 0.7,P< 0.01), lifetime single marital status (OR = 0.45,P< 0.01), and substance abuse in the last year (OR = 0.35,P< 0.01), whereas it was more frequently associated with a major number of lifetime major depressive episodes (OR = 1.78,P< 0.01) and psychiatric visits in the last year (OR = 1.38,P= 0.01).ConclusionFew significant differences were found between genders in BD, particularly for those clinical features that are associated with poor prognosis (substance abuse for males and number of depressive episodes for females). Transcultural studies are needed to identify cultural versus illness-related variables possibly explaining the different clinical presentation of BD in relation to gender.