This study aimed to identify factors associated with severe injury and mortality from road traffic accidents (RTA) among motorcycle and car users in southern Thailand. The data were obtained from the Office of Disease Prevention and Control, Thailand, for years 2008-2013. Chi-squared tests were used to assess associations between determinants and outcomes and these associations were then estimated after adjusting for possible confounding with other factors using logistic regression. Severe injury and mortality contributed 11.6% and 5% to RTA of motorcycle users, and 14.3% and 7.5% for car users. Among motorcycle users, male gender, older age, and not wearing a helmet increased severe injury and mortality rates, whereas drivers had more severe injuries than passengers. Older car users had higher severe injury and mortality rates, whereas not fastening seat belts had higher mortality. Safety device use should be made mandatory for both drivers and passengers. Male motorcycle users and the elderly should be focused on.