Background. Childhood injury is a major public health issue in many parts of the world, contributing significantly to paediatric morbidity and mortality. World Health Organization recently projected that with the current trends, trauma and infectious diseases will account for equal numbers of year of potential life lost worldwide by the year 2020. Aim. This study aimed to investigate factors predictive of childhood injury mortality. Design. A prospective hospital-based cross-sectional study. Methods. All attendances and admissions to the Children’s Emergency Room at the Wesley Guild Hospital, Ilesa, Osun State, Nigeria, over a period of 2 years (1 June 2007 - 30 May 2009) were serially documented and all patients with injury were recruited into the study. The socio-demographic variables, injury characteristics, Pediatric Trauma Score (PTS) and Glasgow Coma Score (GCS) were tested against outcome by binary logistic regression analysis. Results. Five hundred and seventy-six children presented with injury during the study period with 22 deaths, giving an injury mortality rate of 3.8%. Logistic regression modelling found infancy (odds ratio (OR) 1.14, 95% confidence interval (CI) 0.04 - 0.37), head injury (OR 2.51, 95% CI 0.10 - 0.61), low PTS (≤8) (OR 8.95, 95% CI 0.86 - 0.94) and low GCS (<9) (OR 5.22, 95% CI 0.40 - 0.69) to be significant independent predictors of childhood injury mortality. Conclusion. Prompt identification of the above factors in children with injury may prevent many deaths.