Few studies have examined school-based factors associated with variability in the victimization and health of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth. Among 15,965 students in 45 Wisconsin schools, we identified differences based on Gay-Straight Alliance (GSA) presence. Youth in schools with GSAs reported less truancy, smoking, drinking, suicide attempts, and sex with casual partners than those in schools without GSAs, with this difference being more sizable for LGBTQ than heterosexual youth. GSA-based differences were greatest for sexual minority girls on reported sex while using drugs. GSA effects were nonsignificant for general or homophobic victimization, grades, and school belonging. Findings suggest that GSAs could contribute to attenuating a range of health risks, particularly for LGBTQ youth. (Contains 3 tables and 1 figure.)