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Background The risk for cardiovascular events associated with systemic therapies for psoriasis, including biologics, is unclear.Methods We used administrative data from Medicare 2006 through 2011 to identify psoriasis patients who initiated systemic treatments. We estimated incidence rates of hospitalized myocardial infarction, stroke, and a composite cardiovascular disease outcome, adjusting for potentially confounding factors.Results There were 28,878 initiations of psoriasis treatments. Rates of myocardial infarction were highest for methotrexate (10.32/1000 patient-years, 95%CI 8.55–12.46) and numerically lower for biologics. Patterns were similar for stroke and the composite cardiovascular disease outcome. After multivariable adjustment, there were no significant differences between systemic therapies for any of the outcomes studied.Conclusions In this cohort of predominantly older psoriasis patients, there was neither an elevated nor a protective effect on cardiovascular or stroke events associated with systemic therapies for psoriasis compared to conventional treatments.