Background: Argentina, Brazil, and Uruguay are the Latin American countries with more HIV cases among injecting drug users (IDUs). High HIV seroprevalence was also found among non-injection drug users (NIDUs).Vulnerability within drug using populations is related to epidemiological, cultural, political, and legal factors that have been addressed by a project financed by Brazil?s Council on Scientific and Technological Development (#014-490426/2006-9). The objective for this abstract is to analyze, in a descriptive/exploratory way, socio-demographic data, HIV seroprevalence, and risk practices of drug users, from thirteen cross-sectional studies from different cities of Argentina, Brazil, and Uruguay (1998-2004), restructured and merged.Methods: A comprehensive database with 3604 records was created, using all available data belonging to IDUs, ex-IDUs, and NIDUs from the three countries.Results: The sample was 79.6% male and the median age was 28 years old. 55.6% reached up to 7 years of formal education; only 52.5% had a job; and 33.5% had been imprisoned some time in their lives. 70.4% of the cases were IDUs or ex-IDUs, and most were cocaine users.3041 HIV serologies were carried out, resulting in a seroprevalence of 22.8%. The mean age of those who were positives (31.5 years old) was significantly greater than those who were negatives (28.7 years, p < 0.001). There was no statistically significant difference between men (22.8%) and women (22.6%). The seroprevalence among IDUs was 29.4% in contrast to 7.6% among NIDUs (p < 0.001). 55.3% of IDUs had shared injection materials at some time in their lives.Conclusions: A high HIV seroprevalence among drug users (especially among IDUs, but in some extent among NIDUs) was confirmed. This analysis shows similar situations of vulnerability in the three countries. It is necessary to maintain programs aiming to decrease associated drug-related harms and to curb the spread of HIV/AIDS among IDUs/NIDUs.