Abstract Every year, about 1.3 million people die on the world’s roads. The aim of the study was to analyze the mortality trends from traffic injuries, and to discuss strategies for the prevention of road traffic injuries and road safety promotion in Lithuania. A longitudinal study was conducted, and regression analysis was applied. The study showed that, when analyzing the changes in mortality from the main causes of death over 2009-2019, the greatest progress in mortality reduction was observed in the category of deaths from external causes; whereas, the number of deaths from diseases of the circulatory system did not change, and the number of deaths from malignant tumors increased slightly. In Lithuania, the death rate from traffic injuries per 100,000 inhabitants decreased significantly over a 50-year period (1971-2020) (in the whole population, and in the subgroups of men and women). In Lithuania, during the fifty-year period (1971-2020), pedestrian mortality rates decreased significantly in the whole population, and children and adolescents (0-14, 15-19, and 0-19 years). Over 1998-2020, road traffic injury deaths decreased significantly in children age groups 0-14, 15-19, and 0-19. After exploring the preventive strategies used for road safety promotion, it was revealed that the most effective results were achieved, when education, safe environment creation, and legislation with enforcement were used. It was important to create a safe engineering environment, to separate pedestrian and bicycle paths from high-speed traffic on roads, to improve the visibility of road users, to apply measures that reduce driver’s fatigue, and to combat the usage of mobile phones while driving. Preventive activities were aimed at alcohol control, speed limitation, education of safe behavior of drivers, promotion of safe cars operation. The usage of safety belts and safety seats, helmets for motorcyclists and cyclists were increased through legislative and educational measures.