This study was to determine the prevalence and socio-demographic associated factors for serious injury among adolescents in Malaysia. The study used data from the Malaysian Global School-based Health Survey which was conducted in 2012. Logistic regression analysis was used to establish associations. Of the 25,507 respondents, 34.9% (42.1% males and 27.8% females) reported having been in a serious injury. Compared to participants who were not bullied, those who reported being bullied were more likely to have sustained serious injury (aOR = 2.2; 95% CI [1.95 - 2.48]). Adolescents who were involved in physical fighting were 57.5% (aOR = 2.75; 95% CI [2.53 - 2.99]) and more likely to have sustained serious injury compared to those who were not involved in the fighting. Meanwhile, adolescents who used substances were 52.3% (aOR = 1.68 [1.52 - 1.85]) and more likely to have sustained serious injury compared to those who did not use substances. Serious injury is frequent among adolescents in Malaysia. Based on studies by Harel, suggestion where reduction of substance use and bullying may be assessed if they have an impact in reducing serious injury among adolescents. Furthermore, educational programmes that focus on the underlying causes and determinants of injury provide an effective and efficient method of injury prevention.