Rabies is a viral zoonotic disease caused by the lyssavirus and endemic to most tropical and sub-tropical areas of the world. This study reports on the occurrence of rabies in humans and dogs and relates the results to the vaccination status of the dogs. A total of each of 25 brain and saliva samples of dogs were tested for Lyssavirus using RT-PCR and visualised using gel electrophoresis. Additionally, histopathological diagnosis of the Lyssavirus was made on the brain samples. A lyssavirus positivity of 34 % was realised. Sample specific positivity was 58 % and 10 % for brain and saliva samples respectively. Only one of the nine vaccinated dogs tested positive for lyssavirus. Five dogs that tested positive for the virus had bitten seven people prior to death. Results confirms the endemicity of the virus in Ghana and the danger it poses to humans. This study confirms vaccination as an effective tool for preventative of rabies. However, elimination of the disease is possible if there is an established and effective collaboration between veterinary and human medicine through one health.