Objective: This study investigated gender differences in the role of appraisals of safety in the relationship between exposure to violence and trauma-related symptoms among South African adolescents living in low socioeconomic settings. Limited research exists in developing contexts on the role of cognitive appraisals in mitigating outcome following exposure to violence. Given the prevalence of violence in South Africa and the vulnerability of youth, this type of research is valuable in identifying adolescents at risk of negative psychological outcome following exposure, and in informing intervention efforts. Method: Adolescents (N = 498) completed an adapted version of the Harvard Trauma Questionnaire (Mollica et al., 1992) and the Safety Index (Ward, Flisher, Zissis, Muller, & Lombard, 2001). Results: The results indicate a significant positive relationship between all violence subscales and trauma-related symptoms, whereas a significant negative relationship was found between sense of safety and trauma-related symptoms. Important gender differences were identified in the role of appraisals of safety, with more effects noted for women than men. For men, the obtained results only demonstrated a health-sustaining role. For women, the results indicated a health-sustaining role, an indirect effect, and a stress-reducing role. Conclusion: These findings stress the necessity of gender-specific interventions. Assessment of psychological trauma, particularly among female adolescents, needs to include measures of cognitive appraisals related to safety. Therapeutic techniques that may be particularly beneficial to adolescent girls are those focusing on promoting sense of safety and targeting dysfunctional threat appraisals.