To better elucidate the incidence, characteristics, and consequences of transport-related injuries in a less developed country in Africa, we undertook an epidemiologic survey in Ghana. A total of 21,105 persons were surveyed, in both an urban area (Kumasi, n = 11,663) and a rural area (Brong-Ahafo, n = 9442). In the preceding year, a total of 656 injuries were reported in the urban area and 928 injuries reported in the rural area. Transport-related mechanisms accounted for 16% of all injuries in the urban and 10% of all injuries in the rural area. The annual incidence of transport-related injuries was almost identical in the two settings, 997/100,000 persons in the urban area and 941/100,000 in the rural area. In both settings, transport-related injuries were more severe than other types of injuries in terms of mortality, length of disability, and economic consequences. In the urban area, the most common transport-related mechanisms were either to passengers involved in crashes of mini-buses or taxis (29%) or to pedestrians struck by these vehicles (21%). In the rural area, the most common transport-related mechanisms were bicycle crashes. The second most common rural mechanisms were motor vehicle crashes, which were the most severe and which involved commercial (83%) rather than private vehicles. Prevention strategies need to be different from those in developed countries and should target commercial drivers more than private road users.