Background: Urban centers across Canada and the United States have battled syphilis epidemics with high rates of human immunodeficiency virus (HIV) coinfection for over a decade. We examined the spatial epidemiology of syphilis over time for Toronto (Canada) with the intention of forming new insights and strategies for restoring low syphilis rates., Methods: Syphilis incidence rates, HIV-syphilis coinfection, and sexual risk behavior prevalences were estimated and mapped from primary, secondary, early latent syphilis cases reported to Toronto Public Health between January 1, 2006, and December 31, 2010, using ArcGIS 9.0. Geographic clusters of significantly elevated syphilis incidence rates were identified using SaTScan 9.0. The relationship between syphilis incidence rates and sociocultural factors was modeled using the Besag, York, and Mollie model., Results: Between 2006 and 2010, syphilis incidence rates were high in Toronto's downtown core area, intensified, and spread outward initiating 3 independent outbreak areas. HIV coinfection was high (47%); however, no spatial clustering was identified. Syphilis incidence rates, HIV coinfection, and behavioral risk factors promoting sexually transmitted infection transmission were high outside the core area, suggesting that peripheral sexual networks may be influencing high syphilis infection rates both inside and outside the core., Conclusions: Toronto's syphilis epidemic is mature. Response, resources, and intervention activities should target core and noncore areas.