Latin America is the world region with the highest rates of youth tobacco use and widest socioeconomic gaps, yet no data are available on smoking among Indigenous people, the largest disadvantaged group in the region. A self-administered survey of 3,131 8th grade youth enrolled in a random sample of 27 urban and rural schools was administered in 2004 in Jujuy, Argentina. Standard questions adapted from global surveys were used. Compared with youth of European background (11.4%; 95% CI 6.7-15.1), Indigenous (23.0%; 95% CI 21.0-25.0), and Mixed ethnicity (23%; 95% CI 18.9-27.1) youth had higher prevalence of current smoking. The odds of current smoking remained significantly elevated for Indigenous (OR 1.9; 95% CI = 1.1-3.3) and Mixed youth (OR 2.0; 95% CI 1.2-3.4) after controlling for confounders. Other risk factors that were associated with current smoking included: having any friends who smoke, repeating a grade in school, depressive symptoms in previous year, drinking any alcohol in the previous week and thrill seeking orientation. These results underscore the importance of social and cultural diversity aspects of the global tobacco epidemic.