Few studies have examined the early development of a broad range of health issues of importance in adolescence in Latina (female) youth, despite their being potentially a vulnerable group. This study compared suicide and depressive symptoms, substance use, violence exposure, injury prevention, obesity, and health-related quality of life among Latina, African-American, and white females as well as Latino (male) youth in fifth grade, as well as differences related to immigrant generational status for Latinas.Data were from the Healthy Passages study, including 3,349 African-American, Latina, and white females as well as Latino male fifth graders in three U.S. metropolitan areas. Self-report items and scales were used to compare status on health-related issues. Generational status was classified based on the parent report of birth location. Logistic and linear regression analyses were conducted, including adjustment for sociodemographic differences.Latinas showed higher vulnerability than white females for several health issues, whereas few remained after adjustments for sociodemographic differences (higher obesity, lower bike helmet use, and lower physical health-related quality of life). Latina's lower vulnerability compared with African-American females generally persisted after adjustments. Third generation Latinas, after adjustments, reported lower prevalence of alcohol use and fewer friends using alcohol, yet higher future intentions of alcohol use, than first and second generation Latinas. There were few differences between Latina and Latino youth.Latina youth generally report low vulnerability across health issues in preadolescence. To the extent they appear at higher vulnerability than white females, this may be related to their disadvantaged sociodemographic status.