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There is limited, if any, prior research exploring the potential link between adolescents’ safety concerns and their predisposition to possess weapons has been limited. This study aimed to examine the relationship between high school students’ perceived lack of safety and their weapons carrying behavior in a multiyear nationally representative sample of high school students. Information on self-reported weapons carrying in past month and gun carrying in past year, perceived lack of safety at school or during commute, being bullied and/or threatened, involvement in physical fights, and demographic characteristics were retrieved from Youth Risk Behavior Surveillance Survey data for 1991-2017. Generalized linear mixed models were used to address data clustering by survey year. Sampling design and sample weights were accounted for. Of a total number of 195,280 respondents with valid responses during 1991-2017, 18%, 7%, and 5%, respectively, carried weapon(s) in general, weapon(s) to school, and gun. On an average, 5% skipped school due to safety concerns. Missing ≥2 school days was associated with weapon (adjusted odds ratio [AOR]: 2.25; 95% confidence interval [CI]: 1.94 -2.61) and gun (AOR: 3.18; 95% CI: 1.81 -5.58) possessions, as well as weapons possession in school (AOR: 2.47; 95% CI: 1.96 -3.12). Experiences of weapons-induced injury(ies) or threat(s), and involvement in physical fights were other significant covariates in adjusted analyses. Compared with non-Hispanic whites, students of other racial/ethnic groups had significantly lower odds of possessing weapons. Perceived lack of safety emerged as a potential determinant of weapon carrying, a behavior with far-reaching public health concerns. While future research looking into the psychological motivations of possessing weapons is recommended, our findings offer a unique opportunity to address the crucial problems of school absenteeism induced by experiences of aggression and fears for safety as well as preempt the consequences of weapons-possession by adolescents.