OBJECTIVES:  Major Depressive Disorder (MDD) has been cited as one of the leading causes of disabilities worldwide.   This analysis seeks to explore the prevalence of MDD across select geographies and to compare the profile of sufferers. METHODS:  Data were taken from the US, Brazil, and Japan 2011 National Health and Wellness Survey, a cross-sectional Internet-based survey representative of the adult population.  Patients were classified as having MDD using the Patient Health Questionnaire (PHQ9).  Health-related quality of life (HRQoL) was assessed with the SF-12 Health Survey (SF-12v2), and activity impairment was measured with the Work Productivity and Activity Impairment questionnaire (WPAI).   Comparisons between patient groups were made with chi-square tests for categorical variables and ANOVA for continuous variables. RESULTS: Prevalence of MDD differs significantly across geographies, with Brazil having the highest percentage (9.8%, 13.5 M) followed by US (7.1%, 16.2 M ) and Japan (4.7%, 5.0 M).  In US and Brazil, MDD sufferers were more likely to be women than non-sufferers and were significantly younger (ps<0.05).  Sufferers in US, Brazil, and Japan were more likely to experience insomnia/sleep difficulties and anxiety than non-sufferers (p<0.05).  In each geography, MDD sufferers had a significantly lower mental QoL compared to the non-sufferer population, but the association was strongest in Japan (28.5 vs. 31.9 in the US vs. 35.4 in Brazil; p<0.05).  In US, MDD sufferers reported greater work and activity impairment (42.0% and 51.3%, respectively vs. 12.2% and 18.2% for non-sufferers, respectively; ps<0.05).  In all geographies, MDD sufferers had more ER visits in the past six months relative to non-sufferers (p<0.05) with the highest proportion in Brazil (35.8%).  Hospitalization among MDD sufferers was also highest in Brazil (15.7%). CONCLUSIONS: Cross-country comparisons of MDD can provide insights to the magnitude of the problem and assess disease burden among these sufferers.