Background: Bipolar disorder is associated with an increased burden of general medical conditions that might be related to a more severe illness course. Methods: This is a cross-sectional study that evaluated clinical correlates of general medical comorbidities in outpatients with bipolar disorder (BD) involving 203 adult patients with a DSM-IV diagnosis of BD, consecutively recruited from the Bipolar Research Program (PROTAHBI) in Porto Alegre, Brazil. Clinical, demographic and anthropometrical variables were systematically assessed, and general medical comorbidity was measured using the Cumulative Illness Rating Scale (CIRS). Results: The prevalence of one or more medical comorbidities was 90.1%. The most common were those from endocrine/metabolic/breast, neurologic and vascular categories. A high burden of general medical comorbidities (defined as CIRS total score ≥ 4) was related to increasing age and body mass index and longer duration of illness after controlling for confounding factors. Limitations: The cross-sectional design limits our ability to make causal conclusions. Also, our sample consisted of patients with longer illness duration from a tertiary clinic and may not generalize to the whole spectrum of bipolar disorder. Conclusions: BD was associated with a high burden of general medical conditions related to age, obesity and longer duration of illness. Medical comorbidities must be incorporated as a core feature in the development of effective treatment strategies for bipolar disorder