Background: Reliable mortality statistics are key for national health information systems, population health assessment, health policy and service planning; and programme evaluation. The Medical Certificates of Cause of Death (MCCDs) are major sources of this information. The aim of this study was to determine the underlying causes of deaths in Northern Ghana, by reviewing duplicate copies of MCCD, at the TTH. Methods: A total of 2,134 duplicate copies of the MCCD were reviewed. Data was analysed by age, gender and underlying cause of death. Associations were determined using Fisher’s exact test. Results: The major underlying causes of deaths were: NonCommunicable Diseases (NCDs) (50.0%), Communicable Diseases (CDs), (29.3%) and injuries (20.7%). The mean age (years) for the study population was 48.2±20.8 and that, majority (78.1%) were males (P<0.0001). The top five CDs were: Viral hepatitis (39.4%), HIV/AIDS (12.4%), lobar pneumonia (11.0%), diarrhoea diseases (10.5%) and peptic ulcer disease (8.8%). The common NCDs were: Cardiovascular disorders (49.2%), cancers (20.5%), metabolic (11.2%) and renal disorders (9.4%). The common injuries related deaths were; RTA (80.7%), alcohol (9.5%) and burns and explosions (3.9%). The top 10 specific underlying causes of death were: arterial hypertension (20.1%), RTA (16.7%), Viral hepatitis (11.6%), cancers (10.4%), diabetes mellitus (5.2%), end stage kidney disease (4.5%), HIV/AIDS (3.7%), bacterial pneumonia (3.2%), diarrhoea diseases (3.1%) and peptic ulcer disease (2.7%). Conclusion: NCD were the commonest major underlying cause of death. All the deaths were common in males. The common specific underlying causes of death were: arterial hypertension, RTA, Viral hepatitis, cancers, DM, and ESKD.