Little is known about the factors underlying the striking increase in overweight occurring between first and second generation US immigrants. Using data from the National Longitudinal Study of Adolescent Health, this study addressed two goals. First, we determined which measures of acculturation (defined as the acquisition of dominant cultural norms by members of a non-dominant group) were important. Second, we determined how the acculturation process affected differences in overweight and its proximate determinants (e.g., physical activity, diet, and smoking) as immigrants acculturated to American society. In addition, we sought to elucidate the role of underlying structural factors (e.g., family income and crime) and acculturation factors (e.g., language spoken at home and proportion of foreign-born neighbors) in generation differences in overweight. Results showed clear structural and acculturation differences between foreign and US-born immigrants to the US. Foreign-born immigrants were more likely to have lower family income and maternal education, and to live in areas of higher immigrant density and greater linguistic isolation. In addition, results suggested rapid acculturation of overweight-related behaviors, such as diet, smoking, and inactivity, in US-born relative to foreign-born immigrants. Multivariate analysis indicated that longer US residence was associated with increased overweight among Puerto Ricans and Cubans. Predicted probabilities showed that controlling for acculturation and proximate factors increased overweight among foreign-born adolescents, but had minimal impact for US-born adolescents. Thus, without the beneficial pattern of: acculturation factors, diet, and physical activity, first generation Hispanic adolescents would have higher overweight prevalence. We found important generation differences in structural, acculturation, and proximate overweight determinants. These lifestyle differences between foreign- and US-born Hispanic adolescent immigrants are likely to underlie the striking increase in overweight prevalence between first and subsequent generation of US residence.