Abstract Background Road traffic accidents (RTAs) pose a public health and development challenge and greatly affect the human capital development of every nation. This study determines the effects of RTAs on households and employers of RTA victims. It identifies factors that influence RTAs as well as the trends of deaths from RTAs in the Kassena Nankana districts (KNDs) in northern Ghana. Methods Victims of RTAs were identified through household visits by the Navrongo Health and Demographic Surveillance System. In all, 123 RTA victims; 101 non-accident victims matched by age, sex, and location; and five key employers in the KNDs were interviewed. Individuals aged 15–59 years who died from RTAs as reported in verbal autopsy data between 2006 and 2011 were used to assess trends in RTA deaths. Knowledge, attitude, and practices about RTAs were compared between the victims and non-victims of RTAs. Socioeconomic statuses of victims and non-victims of RTAs were compared. Cost of RTAs to households and employers was determined by interviewing victims of RTAs in their households and employers on direct and indirect cost incurred during the accident period. Findings The average costs of RTAs to the household and employer were US$6007 and $7625, respectively. The annual mean cost of a RTA to a poor household was $49, representing 183% of its annual income; this cost represents only 5% of the average income of a rich household. There was an increasing trend of deaths due to RTAs, from 7·4% (95% CI 4·1–10·7) in 2006 to 10·9% (3·6–18·3) in 2011. Careless driving, indiscriminate crossing, mechanical fault, loss of control whilst driving/riding, and occupational status were the key determinants of RTAs in the area. Interpretation RTAs impose a substantial economic burden on victims, particularly the poor. The importance of the problem of RTAs warrants immediate interventions to reduce road traffic crashes in the districts. Funding The Navrongo Health Research Center partly funded the project for the data collection. The rest of the funding was from personal savings.