Increases in bicycling in the United States results in increased exposure to crashes and injuries. This research focuses on the factors involved in bicycle crashes in the United States and the state of Iowa. Data from the U.S. Nationwide Inpatient Sample and the Iowa Department of Transportation were used to address three aims: 1) estimate the burden and examine the outcomes of bicycle crashes resulting in hospitalizations nationwide by motor vehicle involvement, 2) describe how bicycle motor vehicle crashes vary by intersection and non-intersection in Iowa, and 3) identify the impact of on-road bicycle facilities on bicycle-motor vehicle crashes in Iowa. Using the U.S. Nationwide Inpatient Sample, years 2002-2009, the estimated annual burden of injury from bicycle-related hospitalizations equated to a billion dollars in hospital charges, over 100,000 days in the hospital, and over 300 in-hospital deaths. We also found that bicycling crashes involving motor vehicles had more hospital charges, longer stays, and greater odds of in-hospital death. We also used the Iowa Department of Transportation crash database, 2001 to 2010, to examine risk factors for bicycle-motor vehicle (BMV) crash locations. We found that BMV crashes involve risk factors at person, crash, environment, and population levels and these vary by intersection and non-intersection. Compared to intersections, non-intersection crashes were more likely to involve young bicyclists (0-9 years), locations outside city limits, with driver vision obscured, reduced lighting on the roadway and less likely involve failure to yield right of way. Finally, we conducted a case site-control site study in Iowa, using crash data from 2007 to 2010 to investigate the impact of pavement markings (bicycle lanes and shared lane arrows) and bicycle-specific signage on crash risk. Our results suggest that bicycle facilities are protective against crashes, with the most protective being the combination of both pavement markings and signage, followed by pavement markings alone, and then signage alone. This project shows that bicycling carries a large burden of injury in the United States and that there are many contributing factors to bicycle crashes. It also provides evidence suggesting that infrastructure changes can decrease crash occurrence and there opportunities to intervene at other levels (e.g., person factors) to have an even greater impact overall.