Over 90% of the annual 1·35 million worldwide deaths due to road traffic injuries (RTIs) occur in low-income and middle-income countries (LMICs). For this Series paper, our aim was two-fold. Firstly, to review evidence on effective interventions for victims of RTIs; and secondly, to estimate the potential number of lives saved by effective trauma care systems and clinical interventions in LMICs. We reviewed all the literature on trauma-related health systems and clinical interventions published during the past 20 years using MEDLINE, Embase, and Web of Science. We included studies in which mortality was the primary outcome and excluded studies in which trauma other than RTIs was the predominant injury. We used data from the Global Status Report on Road Safety 2018 and a Monte Carlo simulation technique to estimate the potential annual attributable number of lives saved in LMICs. Of the 1921 studies identified for our review of the literature, 62 (3·2%) met the inclusion criteria. Only 28 (1·5%) had data to calculate relative risk. We found that more than 200 000 lives per year can be saved globally with the implementation of a complete trauma system with 100% coverage in LMICs. Partial system improvements such as establishing trauma centres (>145 000 lives saved) and instituting and improving trauma teams (>115 000) were also effective. Emergency medical services had a wide range of effects on mortality, from increasing mortality to saving lives (>200 000 excess deaths to >200 000 lives saved per year). For clinical interventions, damage control resuscitation (>60 000 lives saved per year) and institution of interventional radiology (>50 000 lives saved per year) were the most effective interventions. On the basis of the scarce evidence available, a few key interventions have been identified to provide guidance to policy makers and clinicians on evidence-based interventions that can reduce deaths due to RTIs in LMICs. We also highlight important gaps in knowledge on the effects of other interventions.