BACKGROUND: Birth asphyxia is one of the leading causes of neonatal mortality worldwide. In Uganda, it accounts for 28.9% of all neonatal deaths. With a view to inform policy and practice interventions to reduce adverse neonatal outcomes, we aimed to determine the prevalence and factors associated with birth asphyxia at two referral hospitals in Northern Uganda. METHODS: This was a cross-sectional study, involving women who gave birth at two referral hospitals. Women in labour were consecutively enrolled by the research assistants, who also attended the births and determined Apgar scores. Data on socio-demographic characteristics, pregnancy history and care during labour, were obtained using a structured questionnaire. Participants were tested for; i) malaria (peripheral and placental blood samples), ii) syphilis, iii) white blood cell counts (WBC), and iv) haemoglobin levels. The prevalence of birth asphyxia was determined as the number of newborns with Apgar scores < 7 at 5 min out of the total population of study participants. Factors independently associated with birth asphyxia were determined using multivariable logistic regression analysis and a p-value < 0.05 was considered statistically significant. RESULTS: A total of 2,930 mother-newborn pairs were included, and the prevalence of birth asphyxia was 154 [5.3% (95% confidence interval: 4.5- 6.1)]. Factors associated with birth asphyxia were; maternal age ≤ 19 years [adjusted odds ratio (aOR) 1.92 (1.27-2.91)], syphilis infection [aOR 2.45(1.08-5.57)], and a high white blood cell count [aOR 2.26 (1.26-4.06)], while employment [aOR 0.43 (0.22-0.83)] was protective. Additionally, referral [aOR1.75 (1.10-2.79)], induction/augmentation of labour [aOR 2.70 (1.62-4.50)], prolonged labour [aOR 1.88 (1.25-2.83)], obstructed labour [aOR 3.40 (1.70-6.83)], malpresentation/ malposition [aOR 3.00 (1.44-6.27)] and assisted vaginal delivery [aOR 5.54 (2.30-13.30)] were associated with birth asphyxia. Male newborns [aOR 1.92 (1.28-2.88)] and those with a low birth weight [aOR 2.20 (1.07-4.50)], were also more likely to develop birth asphyxia. CONCLUSION: The prevalence of birth asphyxia was 5.3%. In addition to the known intrapartum complications, teenage motherhood, syphilis and a raised white blood cell count were associated with birth asphyxia. This indicates that for sustained reduction of birth asphyxia, appropriate management of maternal infections and improved intrapartum quality of care are essential.