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Injuries among adolescents pose significant public health problems. Unintentional injuries are the leading cause of adolescents’ mortality and disability with the largest burden in low-and middle-income countries. Yet, there is paucity of data in Ghana on adolescent injuries. The present study aimed to determine the prevalence and correlates of unintentional injuries among in-school adolescents in Ghana using data from the Global School-Based Health Survey. Cross-sectional data on 2058 adolescents in junior and senior high schools who randomly participated in the 2012 Global School-Based Health Survey were analyzed. Descriptive statistics were performed to determine the prevalence of unintentional injuriesacross the background characteristics of in-school adolescents. Binary logistic regression was employed to determine the factors associated with unintentional injuries. The results were presented as crude and adjusted odds ratios at a 95% confidence interval. The prevalence of one or more serious injuries in the past 12 months was 57.0%. The most commonly reported type and cause of injuries were “I had a cut or stab wound” (15.2%) and “I fell” (13.1%), respectively. In the adjusted regression, in-school adolescents aged 14–16 (aOR = 1.60, CI = 1.12–2.28) were more likely to report one or more serious injuries compared to their counterparts aged 13 or younger. In-school adolescents who participated in physical education (aOR = 1.27, CI = 1.03–1.58) had higher odds of reporting one or more serious injuries. The odds of being injured was higher among adolescents who were truant at school compared to those who were not truant (aOR = 1.42, CI = 1.14–1.77) In-school adolescents who were bullied were more likely to report being injured one or multiple times compared to their counterparts who were not bullied (aOR = 2.16, CI = 1.75–2.65). In addition, the odds of being injured once or multiple times were higher among adolescents who were physically attacked (aOR = 2.21, CI = 1.78–2.75), those that engaged in physical fighting (aOR = 1.94, CI = 1.54–2.45), and those who reported high psychological distress (aOR = 2.00, CI = 1.52–2.63) compared to their counterparts who were not. Conversely, adolescents in senior high schools were 39% less likely to be injured once or multiple times compared to those in junior high schools (aOR = 0.61, CI = 0.47–0.79). A relatively high prevalence of unintentional injuries was found among in-school adolescents in the study. The numerous factors identified in this study could be integrated into health promotion and injury prevention activities to help reduce the occurrence of injuries among in-school adolescents. Moreover, students who are susceptible to unintended injuries such as older adolescents, victims of bullying, those who participate in physical education, those who are often involved in fights, truants, and those who have psychological distress should be sensitized to take measures that will reduce their level of susceptibility. First aid treatment services should also be made available in schools to treat victims of unintended injuries.