Tissue plasminogen activator (tPA) was approved by the Food and Drug Administration for ischemic stroke treatment since 1996 at the United States of America and also 2002 at Taiwan. Since after it is strongly advertised for a promising benefit to early thrombolysis that is further echoed by a recommendation in clinical guidelines from multiple medical associations in worldwide. Because of an overwhelming data of positive benefit collected in the evidence-based medicine database, legal dispute subsequently occurs when tPA is failed to be administrated in appropriate time. In order to elucidate the legal viewpoint for tPA used in ischemic stroke, a review of the domestic judiciary decrees regarding this issue was conducted. Cases in Taiwan were executed from the open access database of the Judicial Yuan, Taiwan. The background, legal dispute and judgment of each case were analyzed. Till August, 2010, there were 6 cases in Taiwan. All cases occurred after 2003. The causes of disputes were a loss of chance for thrombolysis due to a delay of diagnosis (4 cases, 67%) and a failure of thrombolytic treatment after a diagnosis of ischemic stroke (2 cases, 23%). All cases were presented to non-neurologists at initial. Five cases expired or terminated into vegetation before litigation. A failure of early diagnosis or treatment after a diagnosis of ischemic stroke are important for medicolegal dispute in tPA usage, which is expected to become prevalent in Taiwan in future. A fatal or poor outcome may be a triggering factor for litigation. Therefore, an improvement of the knowledge and practice to increase early diagnosis of ischemic stroke is the key factor for reducing medicolegal issue regarding tPA use in ischemic stroke. This is particularly true for non-neurologist physicians.