Angiotensin converting enzyme (ACE) influences vessels tone and the coagulation/fibrinolysis system. The ACE gene I/D polymorphism has been linked with PAI-1 and fibrinogen levels and with Factors VII and X activities. Therefore, we aimed to test whether I/D polymorphism could be related to thrombolysis safety and efficacy. We studied strokes involving the middle cerebral artery (MCA) territory of patients who received t-PA <3 h of stroke onset. Blood samples were obtained before t-PA administration to measure fibrinogen, PAI-1, Factors VII and X. I/D polymorphism was determined by polymerase chain reaction and agarose electrophoresis. Recanalization rates were serially evaluated by Transcranial Doppler. Among 96 included patients the genotype frequency was: DD=33.3%, ID=57.3% and II=9.4%. A strong association was found between DD homozygous and successful recanalization rates (DD=69.2%, ID+II=31.6%, p=0.002 at 1 h; DD=91.3%, ID+II=51%, p=0.001 at 6 h; DD=100%, ID+II=72.3%, p=0.003 at 24 h post-t-PA administration). In fact, DD genotype was an independent predictor of recanalization (OR=4.3 95% CI 1.35-13.49, p=0.013). No relation was found between I/D polymorphism and symptomatic hemorrhagic complications (p=0.237). No association between ACE genotypes and Factor VII or Factor X activities, neither with fibrinogen or PAI-1 levels was observed. DD homozygous is strongly associated with MCA recanalization following t-PA treatment. Mechanisms of benefit remain unknown since I/D polymorphism had similar FVII and X activities and PAI-1 and fibrinogen levels in our stroke population.