Background: The early recanalization (ER) of an occluded cerebral artery is important for clinical improvement in acute ischemic stroke. The aim of the study was to assess the possible association between the prior use of antiplatelets (AP) and ER of occluded middle cerebral artery (MCA) after intravenous thrombolysis (IVT). Methods: In 146 consecutive acute ischemic stroke patients presenting with occluded MCA and treated with IVT, the ER and incidence of symptomatic intracerebral hemorrhage (SICH) were compared according to the presence or absence of prior AP use. ER was assessed by transcranial Doppler or digital subtraction angiography within 2 h after the end of IVT. Results: Fifty-six patients (28 males, mean age: 69.8 ± 9.8 years) used AP and 90 patients were AP naïve (51 males, mean age: 65.8 ± 12.5 years). Prior AP use was associated with a higher rate of early MCA recanalization (53.6 vs. 29.5% in AP naïve, p = 0.007) and was shown as a predictor of ER (OR: 2.30, 95% CI: 1.14–4.65; p = 0.020) in unadjusted analysis. No difference was found in the occurrence of SICH. Conclusion: Prior use of AP was associated with a higher rate of ER of occluded MCA, but with no increase of SICH after IVT.