Bias-based aggression at school in the form of homophobic name-calling is quite prevalent among early adolescents. Homophobic name-calling is associated with low academic performance, higher risky sexual behaviors, and substance abuse, among other adverse outcomes. This longitudinal study examined risk and protective factors across multiple domains of the social ecology (individual, peer, family, school and community) and levels of analysis (within- and between-person) associated with homophobic name-calling perpetration and victimization. Students from four middle schools in the U.S. Midwest (N = 1,655; [X-bar] age = 12.75; range = 10-16 years) were surveyed four times (Spring/Fall 2008, Spring/Fall 2009). For homophobic name-calling perpetration, significant risk factors included impulsivity, social dominance, traditional masculinity, family violence, and neighborhood violence; while empathy, peer support, school belonging, and adult support were significant protective factors. For homophobic name-calling victimization, significant risk factors included empathy (between-person), impulsivity, traditional masculinity, family violence, and neighborhood violence, while empathy (within-person), parental monitoring, peer support, school belonging, and adult support were significant protective factors.