Background High global neonatal deaths have triggered efforts to improve facility-based care. However, the outcomes achievable at different levels of care are unclear. This study compared morbidity and mortality patterns of newborns admitted to a regional and a district hospital in Ghana to determine outcome, risk and modifiable factors associated with mortality. Objective This study compared morbidity and mortality patterns of newborns admitted to a regional and a district hospital in Ghana to determine outcome, risk and modifiable factors associated with mortality Methods A cross-sectional study involving a records-review over one year at the Upper West Regional Hospital, and three years at St Joseph's District Hospital, Jirapa was carried out. Age, sex, gestational age, weight, duration of admission, diagnosis, among others were examined. The data were analysed and statistical inference made.