This multicenter study estimated the prevalence of major depressive disorder (MDD) among emergency department patients in Latin America. To identify patients with MDD, we used a combination of DSM IV- criteria interview and a questionnaire screen including the center for Epidemiological Studies Depression Scale. We analyzed data from consecutive adult patients from hospitals in Argentina, Brazil, Chile, Colombia, and Mexico and described the demographic and health status differences between MDD and non-MDD patients. Prevalence of MDD ranges from 23.0 to 35.0%. The estimates are based on a total of 1,835 patients aged 18 years and over, with response rates of 83.0%. Compared to non-MDD patients, MDD patients were more likely to be middle-aged, female, smokers, of lower socioeconomic status, and to report a diagnosis of asthma or arthritis/rheumatism. Multivariate analysis identified a lower level of education, smoking, and self-reported anxiety, chronic fatigue, and back problems to be independently associated with MDD. Our data suggest that the prevalence of MDD is elevated among emergency department patients in Latin American countries. The integration of depression screening into routine emergency care merits serious consideration, especially if such screening can be linked to psychiatric treatment. © 2007 Wiley-Liss, Inc.