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The Millennium Development Goals (MDGs) have led to reductions in child mortality world-wide. This has, invariably, led to the changes in the epidemiology of diseases associated with child mortality. Although facility based data do not capture all deaths, they provide an opportunity to confirm diagnoses and insight into these changes which are relevant for further disease control.To identify changes in the disease pattern of children who died at the Princess Marie Louise Children's Hospital (PML) in Ghana from 2003-2013.A cross sectional review of mortality data was carried out at PML. The age, sex, duration of admission and diagnosis of consecutive patients who died at the hospital between 2003 and 2013 were reviewed. This information was entered into an Access database and analysed using Stata 11.0 software.Altogether, 1314 deaths (3.6%) occurred out of a total of 37,012 admissions. The majority of the deaths, 1187 (90.3%), occurred in children under the age of 5 years. While deaths caused by malaria, malnutrition, HIV infection and diarrhoea decreased, deaths caused by pneumonia were rising. Suspected septicaemia and meningitis showed a fluctuating trend with only a modest decrease between 2012 and 2013. The ten leading causes of mortality among under-fives were malnutrition, 363 (30.6%); septicaemia, 301 (25.4%); pneumonia, 218 (18.4%); HIV infection, 183 (15.4%); malaria, 155 (13.1%); anaemia, 135 (11.4%); gastroenteritis/dehydration, 110 (9.3%); meningitis, 58 (4.9%); tuberculosis, 34 (2.9%) and hypoglycaemia, 27 (2.3%). For children aged 5-9 years, the leading causes of mortality were malaria, 42 (42.9%); HIV infection, 27 (27.6%); anaemia, 14 (14.3%); septicaemia, 12 (12.2%); meningitis, 10 (10.2%); malnutrition, 9 (9.2%); tuberculosis, 5 (5.1%); pneumonia, 4 (4.1%); encephalopathy, 3 (3.1%); typhoid fever, 3 (3.1%) and lymphoma, 3 (3.1%). In the adolescent age group, malaria, 8 (27.6%); anaemia, 6 (20.7%); HIV infection, 5 (17.2%); sickle cell disease, 3 (10.3%) and meningitis, 3 (10.3%) were most common.There has been a decline in the under-five mortality at PML over the years; however, deaths caused by pneumonia appear to be rising. This highlights the need for better diagnostic services, wider HIV screening and clinical audits to improve outcomes in order to achieve further reductions in child mortality and maintain the gains.