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In 2000, a syphilis outbreak was identified in Ireland.A prospective enhanced database was established in 2000. Crude incidence rates for the general population, men who have sex with men (MSM), and HIV-positive MSM were calculated.Three hundred fifty-six cases of infectious syphilis were diagnosed at 1 center. Eighty-five percent of cases were identified as MSM. Crude incidence rates in MSM, ranging in age between 20 and 44 years, peaked in 2001 at 719 cases per 100,000 of the MSM population. A total of 17.4% of cases occurred in HIV-infected individuals. Crude incidence rates of syphilis in HIV-positive MSM in the center increased to 7280 per 100,000. Similar percentages of MSM with and without HIV infection had unprotected anal intercourse (37% and 41%, respectively).High-risk sexual behavior continues among HIV-infected and -noninfected MSM. Crude incidence rates among MSM in Ireland are alarming when compared with other outbreaks.