Purpose: In France, the bicycle’s modal share is stabilizing after a decline; in some of France’s major cities, it has even increased since the 1990s. It is hence relevant to improve the knowledge of the injury risk associated with cycling, compared with other means of transport such as car, walking and powered two-wheeler (PTW) riding. Methods: The injury incidence rates were estimated by the ratio between accident data and mobility (exposure) data. Two accident data sources were used: police data and hospital-based data (outpatients and inpatients) from the Rhône road trauma Registry. This provides four injury categories: all-injury, hospitalization, serious-injury and fatal-injury. Exposure data were estimated from a regional household travel survey (RTS), using three measures of mobility: number of trips, distance traveled and time spent traveling. The survey was carried out from November 2005 to April 2006, on week days, outside school and public holidays; this seasonality was corrected using the 2007–2008 national household travel survey (NTS) that covered an entire year. Only information involving accidents and trips in, and residents of the Rhône County (1.6 million inhabitants, including the city Lyon) were included in our study. Trends of injury rates were also evaluated in Greater Lyon, using previous travel surveys. Results: The PTW riders had the highest all-injury, hospitalization, serious-injury and fatal-injury rates,followed by cyclists, and lastly by pedestrians and car occupants. The rates between men and women seemed similar among pedestrians and among car occupants. For car occupants, pedestrians and cyclists, the age group 18–25 years had higher all-injury rate compared with the age group 25–65 years. On the contrary, the age group ≥65 years seemed to have higher hospitalization and serious-injury rates,compared with the age group 25–65 years. For cyclists, the injury rates seemed higher in non-dense areas than in dense areas. Between 1996–1997 and 2005–2006 and with regards to time spent traveling, the all-injury, serious-injury and fatal-injury rates seemed to have decreased for car occupants and cyclists. Conclusion: The higher risk for PTW riders is confirmed and quantified; it is very high. Decrease in injury rates seems more marked for cyclists; this may indicate the 'safety in numbers' effect. ounter measures for improving road safety could be implemented, especially for vulnerable road user types. However, they will not be sufficient to fill in the gap between the much higher risk for PTW riders and that of car occupants. Exposure-based injury rates can be a tool for monitoring and evaluating the effectiveness of policies and programs, and for comparisons between countries.