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Differences between BD-I and BD-II patients with regard to specific illness characteristics are poorly understood. This study is mainly aimed to compare socio-demographic and clinical characteristics between BD-I and BD-II patients with the goal of clarifying possible predictors of clinical course. The sample of this cohort study is composed of 391 currently euthymic bipolar patients. Participants were all receiving only maintenance treatment; their psychopharmacological regimens and psychopathological conditions were stable at assessment. After univariate analyses, BD-II patients were more likely to be female, had more frequently a recent depressive episode and substance abuse/dependence relative to BD-I subjects. BD-II patients were also less likely to have a positive history of psychiatric conditions in family, psychotic symptoms at first episode, and first depressive illness episode. Moreover, BD-II were older at their illness onset and first treatment than BD-I patients. Furthermore, BD-I were more likely to have higher depressive, manic, anxiety, and symptoms severity than BD-II patients. After logistic regression analyses, being female (OR = 0.289), having psychiatric conditions in family (OR = 0.273), and higher severity of illness at CGI (OR = 0.604) were all significantly associated with BD-II. Additional studies are required to replicate these results, and facilitate the prediction of BD outcomes according to the specified profile.