Bike-sharing systems (BSS) have been implemented in several cities around the world as policies to mitigate climate change, reduce traffic congestion, and promote physical activity. This study aims to assess the health impacts (risks and benefits) of major BSS in Europe.We performed a health impact assessment study to quantify the health risks and benefits of car trips substitution by bikes trips (regular-bikes and/or electric-bikes) from European BSS with >2000 bikes. Four scenarios were created to estimate the annual expected number of deaths (increasing or reduced) due to physical activity, road traffic fatalities, and air pollution. A quantitative model was built using data from transport and health surveys and environmental and traffic safety records. The study population was BSS users between 18 and 64 years old.Twelve BSS were included in the analysis. In all scenarios and cities, the health benefits of physical activity outweighed the health risk of traffic fatalities and air pollution. It was estimated that 5.17 (95%CI: 3.11-7.01) annual deaths are avoided in the twelve BSS, with the actual level of car trip substitution, corresponding to an annual saving of 18 million of Euros. If all BSS trips replaced car trips, 73.25 deaths could be avoided each year (225 million Euros saving) in the twelve cities.The twelve major Bike-sharing systems in Europe provide health and economic benefits. The promotion of shifting car drivers to use BSS can significantly increase the health benefits. BSS in Europe can be used as a tool for health promotion and prevention.