Injuries are a significant cause of death and disability, particularly in low- and middle-income countries. Health care systems in resource-poor countries lack personnel and are ill equipped to treat severely injured patients; therefore, many injury-related deaths occur after hospital admission. This study evaluates the mortality for hospitalized trauma patients at a tertiary care hospital in Malawi. This study is a retrospective analysis of prospectively collected trauma surveillance data. We performed univariate and bivariate analyses to describe the population and logistic regression analysis to identify predictors of mortality. Tertiary care hospital in sub-Saharan Africa. Patients with traumatic injuries admitted to Kamuzu Central Hospital between January 2010 and December 2012. Predictors of in-hospital mortality. The study population consisted of 7559 patients, with an average age of 27 years (±18 years) and a male predominance of 76%. Road traffic injuries, falls, and assaults were the most common causes of injury. The overall mortality was 4.2%. After adjusting for age, sex, type and mechanism of injury, and shock index, head/spine injuries had the highest odds of mortality, with an odds ratio of 5.80 (2.71-12.40). The burden of injuries in sub-Saharan Africa remains high. At this institution, road traffic injuries are the leading cause of injury and injury-related death. The most significant predictor of in-hospital mortality is the presence of head or spinal injury. These findings may be mitigated by a comprehensive injury-prevention effort targeting drivers and other road users and by increased attention and resources dedicated to the treatment of patients with head and/or spine injuries in the hospital setting.