Background. Dora Nginza Hospital had a high neonatal mortality rate (NMR) in 2016. Quality improvement (QI) strategies were subsequently introduced to improve outcomes. Objective. To report changes in the NMR at Dora Nginza Hospital from 2016 to 2019, following the introduction of QI interventions. Methods. A retrospective comparison was conducted of unit-based data from before and after the introduction of QI interventions. Outcomes included total, early and late NMR, NMR by birthweight categories and causes of neonatal deaths. A chi-squared test and relative risk were used to compare groups, with p<0.05 considered significantly different. Results. Total NMR declined from 34.4/1 000 live births to 19.4/1 000 (p<0.01). Early NMR decreased across all birthweight categories (p<0.01). Late NMR decreased in neonates ≥500 g (p=0.02) but not in those ≥1 000 g (p=0.99). Relative risk of early or late neonatal death was 0.57 (0.46-0.69). Total deaths due to prematurity decreased from 108 in 2016 to 39 in 2019 (p<0.01). There was no significant change in deaths due to congenital abnormalities (p=0.051), infection (p=0.1) or intrapartum events (p=0.08). Conclusion. We report a significant reduction in NMR following QI interventions, largely due to a decrease in prematurity-related early neonatal mortality. Similar interventions may be beneficial in other poorly resourced settings. Adequate kangaroo-mother care facilities, availability of nasal continuous positive-pressure ventilation to all preterm neonates, promotion of breastfeeding and protocol-driven management of premature newborns are key.