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Objectives. We compared cycling injury risks of 14 route types and other route infrastructure features. Methods. We recruited 690 city residents injured while cycling in Toronto or Vancouver, Canada. A case-crossover design compared route infrastructure at each injury site to that of a randomly selected control site from the same trip. Results. Of 14 route types, cycle tracks had the lowest risk (adjusted odds ratio [OR] = 0.11; 95% confidence interval [CI] = 0.02, 0.54), about one ninth the risk of the reference: major streets with parked cars and no bike infrastructure. Risks on major streets were lower without parked cars (adjusted OR = 0.63; 95% Cl = 0.41, 0.96) and with bike lanes (adjusted OR = 0.54; 95% CI = 0.29, 1.01). Local streets also had lower risks (adjusted OR = 0.51; 95% Cl = 0.31, 0.84). Other infrastructure characteristics were associated with increased risks: streetcar or train tracks (adjusted OR = 3.0; 95% Cl = 1.8, 5.1), downhill grades (adjusted OR = 2.3; 95% Cl = 1.7, 3.1), and construction (adjusted OR = 1.9; 95% Cl = 1.3, 2.9). Conclusions. The lower risks on quiet streets and with bike-specific infrastructure along busy streets support the route-design approach used in many northern European countries. Transportation infrastructure with lower bicycling injury risks merits public health support to reduce injuries and promote cycling. (Am J Public Health. 2012;102:2336-2343.) [ABSTRACT FROM AUTHOR]