<i>Background:</i> Treatment with tissue plasminogen activator (tPA) is associated with improved outcome in acute ischemic stroke. Of note, a proportion of patients demonstrate rapid and significant neurological recovery within 24 h. This has previously not been systematically studied. We aimed to examine its incidence, predictive factors and correlation with clinical outcomes. <i>Methods:</i> We included 161 patients with acute ischemic stroke who received intravenous tPA within 4.5 h. Patient demographics and clinical data were collected. Rapid neurological recovery was defined as an improvement of at least 50% within 24 h as measured by the National Institute of Health Stroke Scale (NIHSS) score, and long-term outcomes were assessed by 3-month modified Rankin Scale. The incidence of rapid neurological recovery and its correlation with outcomes were studied. The predictors of the phenomenon were examined by univariate analysis. <i>Results:</i> Rapid neurological recovery was present in 44 of the 161 patients (27.3%). This correlated with favorable outcomes at 3 months (p < 0.0005). Lower baseline NIHSS score (p = 0.006), mild (NIHSS score <12) versus severe stroke (NIHSS score ≧12; p = 0.002), normal serum glucose levels on admission (3.3–7.7 mmol/l; p = 0.009) and younger age (p = 0.043) predicted rapid neurological recovery. However, there was no association with time to treatment (p = 0.3). <i>Conclusion:</i> Rapid neurological recovery defines a rapid responder population and was demonstrated in a quarter of patients treated with intravenous tPA. It strongly predicts a good clinical outcome.