A recent study suggests that a high plasma level of tissue plasminogen activator (t-PA antigen) is a risk factor for stroke in men. Whether t-PA antigen is a risk factor for stroke in women is unknown. We measured plasma levels of t-PA antigen in 302 nonselected patients with acute ischemic stroke and in 138 healthy control subjects. In a subgroup of the patients, plasma t-PA antigen was remeasured 6 months after the stroke. Women with acute ischemic stroke (n=171) had median plasma t-PA antigen that was 39% higher than the healthy female control subjects (n=86): 10.3 (8.0 to 13.7) versus 7.4 (6.1 to 9.1) ng/mL (median [interquartile range]), P=.0001. At the reexamination of the patients after 6 months, plasma t-PA antigen was unchanged in the female patients. This suggests that the difference in plasma t-PA antigen between the female patients and the healthy control subjects did not result from an acute phase reaction. In a multivariate regression analysis, high t-PA antigen was an independent risk factor for stroke, and high plasma level of t-PA antigen was associated with severe stroke in women. The current data suggest that plasma t-PA antigen is elevated in women with ischemic stroke.