BACKGROUND: Biking plays a significant role in urban mobility and has been suggested as a tool to promote public health. A recent study has pmposed 2050 global biking scenarios based on large shifts from motorized vehicles to bikes. No previous studies have estimated the health impacts of global cycling scenarios, either future car-bike shift substitutions. OBJECTIVES: We aimed to quantify changes in premature mortality of 2050 global biking scenarios in urban populations from 17 countries. METHODS: Through a quantitative Health Impact Assessment, the mortality risks and benefits of replacing car trips by bike (mechanica bike and electric bike) in urban populations from 17 countries were estimated. Multiple bike scenarios were created based on current transport trends or large shifts from car trips to bike trips. We quantified the estimated change in the number of premature deaths (reduced or increased) concerning road traffic fatalities, air pollution, and physical activity. This study focuses on urban populations between 20 and 64 y old. RESULTS: We found that, among the urban populations (20-64 y old) of 17 countries, 205,424 annual premature deaths could be prevented if high bike-use scenarios are achieved by 2050 (assuming that 100% of bike trips replace car trips). If only 8% of bike trips replace car trips in a more conservative scenario, 18,589 annual premature deaths could be prevented by 2050 in the same population. In all the countries and scenarios, the mortality benefits related to bike use (rather than car use) outweighed the mortality risks. DISCUSSION: We found that global biking policies may provide important mortality benefits in 2050. Current and future bike- vs. car-trip policies should be considered key public health interventions for a healthy urban design.