The effectiveness and safety of intravenous thrombolysis (IVT) in treating patients with acute ischemic stroke (AIS) has been well established. However the total number of patients treated with IVT in Greece is limited. SITS-ISTR (Safe Implementation of Thrombolysis in Stroke- International Stroke Thrombolysis Register) is an international, multicenter study, monitoring the efficacy and safety of IVT in every country. In this article we present data from Greek SITS-ISTR for the last 12 years. We also compare our findings to SITS-MOST (European prospective registry of IVT in AIS) and to SITS-ISTR registry from four other European countries (Italy, Austria, Belgium and Poland). It appears that the number of patients treated with IVT has increased in Greece during the last four years. The majority of Greek AIS patients treated with IVT, show even mild clinical improvement 24 hours after tPA-bolus and the percentage of patients with favorable clinical outcome (mRS 0-2) after 3 months reaches 67.8% [95% Confidence Intervals (CI) 59.8%-74.9%]. The safety of IVT is being evaluated through the number of deaths within 3 months and the frequency of symptomatic intracranial hemorrhages (SICH). The 3 month mortality and SICH rates were 12.3% (95% CI 7.9%-18.7%) and 2.2% (95% CI 0.7%-5.7%) respectively in Greek SITS-ISTR register. In conclusion, our findings are similar to other European countries and underscore the safety and efficacy of IVT for AIS treatment. Additional efforts are needed to further increase the dissemination of IVT in every day clinical practice by providing high-quality training in medical and nursing staff and by promoting the establishment of stroke units in tertiary care stroke centers.