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The increasing number of registered road crashes involving cyclists during the last decade, and the high proportion of road crashes resulting in severe injuries and fatalities among cyclists constitutes a global issue for community health, urban development, and sustainability. Nowadays, the incidence of many risk factors for road crashes of cyclists remains largely unexplained. Given the importance of this issue, the present study has been conducted with the aim of determining relationships between infrastructural, human factors and safety outcomes of cyclists. Objectives: This study aimed, first, to examine the relationship between key infrastructural and human factors present in cycling, bicycle-user characteristics, and their self-reported experience with road crashes. And second, to determine whether a set of key infrastructural and human factors may predict their self-reported road crashes. Methods: For this cross-sectional study, a total of 1064 cyclists (38.8% women, 61.2% men; M = 32.8 years of age) from 20 different countries across Europe, South America and North America, participated in an online survey composed of four sections: demographic data and cycling-related factors, human factors, perceptions on infrastructural factors, and road crashes suffered. Results: The results of this study showed significant associations between human factors, infrastructural conditions and self-reported road crashes. Also, a logistic regression model found that self-reported road crashes of cyclists could be predicted through variables such as age, riding intensity, risky behaviors, and problematic user/infrastructure interactions. Conclusions: The results of this study suggest that self-reported road crashes of cyclists are influenced by features related to the user and their interaction with infrastructural characteristics of the road.