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SummaryAn elevated concentration of the thrombin-antithrombin complex (TAT) has been associated with high mortality rates and poor outcome in ischaemic stroke patients treated with tissue plasminogen activator (t-PA). Moreover, antithrombin drugs have been tested in combination with t-PA in the acute phase of ischaemic stroke to increase treatment efficacy. We aimed to study whether poor outcome associated with TAT among ischaemic stroke patients treated with t-PA could be due to the effects of this complex on recanalisation rates of the middle cerebral artery (MCA) and on haemorrhagic transformation. The TAT levels of 89 patients having a proximal MCA occlusion were measured by ELISA, and the patients were then treated with t-PA. Complete recanalisation was diagnosed by transcranial Doppler (TCD) at 1, 2 and 6 hours post-t-PA infusion and haemorrhagic transformation was identified by computed tomography (CT). Lower levels of TAT were associated with better recanalisation rates at all time-points (1 hour: OR = 24.8 95% CI 1.4–434.8, p = 0.028;2 hours:OR = 6.3 95% CI 1.5–27, p = 0.014; 6 hours: OR = 6.4 95% CI 1.5–26.5, p = 0.011) after adjustment for stroke risk factors. However, no correlation was found between TAT concentration and haemorrhagic transformation. The elevated mortality rates previously observed in patients with high levels of TAT might have been due to revascularisation resistance. Low levels of TAT are not associated with an increase in haemorrhagic complications after t-PA, indicating that the combination of thrombin blockers and t-PA could be a safe and effective treatment for ischaemic stroke in the future.