BACKGROUND: Bipolar disorder presents with diverse clinical manifestations. Numerous investigators have sought to identify variables that may predict a more severe illness course. METHODS: With the objective of studying the clinical characteristics of bipolar patients between South and North America, a comparison was performed between a sample from Argentina (n = 449) and a sample from the United States (n = 503) with respect to demographics and clinical characteristics, including presence of comorbidities. RESULTS: The Argentinian sample had more unfavorable demographics and higher rates of prior psychiatric hospitalization and prior suicide attempt but a better social outcome. However, the sample from the United States had a higher rate of prior year rapid cycling, as well as younger bipolar disorder onset age (mean ± SD, 17.9 ± 8.4 vs. 27.1 ± 11.4 years) and more severe clinical morbidity, though there was no significant difference in terms of the total duration of the illness. Argentinian compared to American patients were taking more mood stabilizers and benzodiazepines/hypnotics, but fewer antipsychotics and other psychotropic medications, when considering patients in aggregate as well as when stratifying by illness subtype (bipolar I versus bipolar II) and by illness onset age (≤21 vs. >21 years). However, there was no significant difference in rate of antidepressant prescription between the two samples considered in aggregate. CONCLUSIONS: Although possessing similar illness durations, these samples presented significant clinical differences and distinctive prescription patterns. Thus, though the Argentinian compared to North American patients had more unfavorable demographics, they presented a better social outcome and, in several substantive ways, more favorable illness characteristics. In both samples, early onset (age ≤ 21 years) was a marker for poor prognosis throughout the illness course, although this phenomenon appeared more robust in North America.