Transgender youth experience negative school environments and may not benefit directly from interventions defined to support Lesbian, Gay and Bisexual (LGB) youth. This study utilized a multi-method approach to consider the issues that transgender students encounter in school environments. Using data from two studies, survey data (total n = 2260, 68 transgender youth) from study 1 and focus groups (n = 35) from study 2, we examine transgender youth’s experience of school harassment, school strategies implemented to reduce harassment, the protective role of supportive school personnel, and individual responses to harassment, including dropping out and changing schools. In both studies, we found that school harassment due to transgender identity was pervasive, and this harassment was negatively associated with feelings of safety. When schools took action to reduce harassment, students reported greater connections to school personnel. Those connections were associated with greater feelings of safety. The indirect effects of school strategies to reduce harassment on feelings of safety through connection to adults were also significant. Focus group data illuminate specific processes schools can engage in to benefit youth, and how the youth experience those interventions.