Road traffic accidents account for 1.35 million deaths and up to 50 million injuries each year globally, mostly among persons aged 5–29 years. The existing road safety measures in Ghana are grossly inadequate, leading to occurrence of unprecedented Road Traffic Accidents (RTA). This study sought to document the epidemiological indices and determine the public health implications of Road Traffic Accidents and the socio-economic effect on lives of RTA victims in Ho and Hohoe Municipalities of the Volta Region in Ghana. A cross-sectional study was carried out among 198 road traffic accident victims who reported to three health facilities in the Volta Region of Ghana. The victims were interviewed using a structured questionnaire. Principal component analysis was done to categorize RTA victims into various economic status. The results show that out of the 198 road traffic accident victims who were interviewed, 50% were breadwinners of their families. Approximately 40% of the accident cases happened between 12 mid-day and 6 o’clock in the evening. Among the RTA cases recorded, 35% involved four-wheeler vehicles. Majority (88%) of those with injuries resulting from motorcycle accidents sustained a head injury; 70% of the respondents who sustained a disability from RTA were unable to perform activity of daily living (i.e. bathing, oral care, and toileting). The average cost of care on RTA victims from formal and informal health care facilities, at the time of this study, was GHC 902 (US$150) and GHC 724 (US$120) respectively. In conclusion, the increase in usage of motorcycles as a means of transport has contributed significantly to the incidence of RTAs in the Ho and Hohoe municipalities posing a public health concern. Majority of RTAs resulted in head injuries and other disabilities which affected their ability to perform activities of daily living and posed significant economic cost to victims and their families who are mostly already in lower wealth quintiles.