Over the past 12 years, Bloomberg Philanthropies (BP) and its partner organisations have implemented a global road safety program in low- and middle-income countries. The program was implemented to address the historically increasing number of road fatalities and the inadequate funding to reduce them. This study evaluates the performance of the program by estimating lives saved from road safety interventions implemented during the program period (2007–2018) through to 2030. We estimated that 311,758 lives will have been saved by 2030, with 97,148 lives saved up until 2018 when the evaluation was conducted and a further 214,608 lives projected to be saved if these changes are sustained until 2030. Legislative changes alone accounted for 75% of lives saved. Concurrent activities related to reducing drink driving, implementing legislative changes, and social marketing campaigns run in conjunction with police enforcement and other road safety activities accounted for 57% of the total estimated lives saved. Saving 311,758 lives with funding of USD $259 million indicates a cost-effectiveness ratio of USD $831 per life saved. The potential health gains achieved through the number of lives saved from the road safety initiatives funded by Bloomberg Philanthropies represent a considerable return on investment. This study demonstrates the extent to which successful, cost-effective road safety initiatives can reduce road fatalities in low- and middle-income countries.