Background: Self-injury has been described as a "silent school crisis," reflecting insufficient knowledge, confusion, lack of effective interventions, and the tendency for adults and youth to shy away from dealing directly with the issue. This purpose of this study was to identify distinct subgroups of youth who may be at increased risk of or reduced risk of nonsuicidal self-injury (NSSI). Methods: The middle-school Youth Risk Behavior Survey was administered in 8 district public middle schools in a large, southeastern county in Florida. A final sample size of 1748, representing approximately 92% of participants who self-reported attendance at 1 of the 8 middle schools (N = 1907) and 74% of the 2350 surveys originally distributed, was used in this study. Chi-squared automatic interaction detection (CHAID) was used to identify distinct segments at risk for or protected from NSSI. Results: CHAID analyses suggested large groups of youth at risk for (and not at risk) having ever tried self-injury including suicidal tendencies, substance use, low belief in life possibilities, and exposure to peer self-injury. Protective factors identified included having low to zero levels of suicidal tendencies, high belief in life possibilities, lack of substance use, and not being a victim of bullying. Conclusion: Engaging adolescents in prevention programs at early stage can reduce the chances of suicidal behavior as well as physical injury. Schools should take the lead in advocating for the development of evidence-based interventions that are capable of addressing factors that contribute to self-injury at multiple levels of youth's environments. (Contains 3 figures and 6 tables.)