Introduction: The recent increase in the use of bicycles and personal mobility devices (PMDs), including mostly E-scooters, is associated with a rapid rise in injuries. Understanding the main crash scenarios leading to these injuries is essential to evaluate and improve preventive and protective measures, especially for PMDs, which are often equated with bicycles. The objective of this study is to identify and compare the most common two-party collision scenarios for bicycles and PMDs, and to identify factors affecting injury severity. Method: Crashes involving at least one PMD or one bicycle and another road user were analyzed from the 2019–2022 French police-reported road crashes database. We investigated the rider, the other vehicle, the road, and the crash scenarios characteristics (pre-crash maneuvers, impact zone on vehicles) and their joint effect on injury severity (hospitalization or fatality: yes/no). Results: We included 16,302 bicycle crashes and 4,118 PMD crashes in the analysis. Most of these collisions (75%) were against a car. The most frequent and the most severe collision scenario was the side-on-head for both bicycles (51%) and PMDs (58%); 67% of both bicycles and PMDs were going straight before the collision. Main factors associated with increased injury severity included colliding with a greater size vehicle, age above 50, and riding on roads with a higher speed limit. Bicycles remained at a higher risk of severe injury than PMDs after accounting for adjustment factors. Conclusions: Although collision scenarios appear similar for bicycles and PMDs, differences in other crash characteristics and injury severity suggest that these two modes of transportation should not be equated in crash investigations. Practical implications: These findings emphasize the need to primarily investigate side-on-head collisions with a moving car for both PMDs and bicycles in order to develop, evaluate, and improve protective devices to reduce the risk of injuries.