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To date, alteplase (tPA) is the only approved treatment for acute ischemic stroke (AIS) within 4.5h of symptom onset in patients meeting all criteria for intravenous thrombolysis. However, previous studies investigating different thrombolytics showed promising results with tenecteplase (TNK). This is a genetically modified tissue plasminogen activator with pharmacological advantages like higher fibrin affinity, longer half-life and more resistance to plasminogen activator inhibitor-1 compared to tPA. This permits a single bolus injection leading to a more convenient administration. This review will first determine the optimal dose of TNK and then compare it to tPA with excellent functional outcome after 90 days as the primary outcome. In addition, neurological improvement, successful recanalization, rate of symptomatic intracranial hemorrhage and 90-day mortality will also be examined. The search for studies was conducted in PubMed and Embase in November 2022, filtered for English-language randomized controlled trials. TNK and AIS were used as MeSH terms which led to 10 randomized controlled trials testing different doses of TNK from 0.1mg/kg up to 0.4mg/kg compared to standard dose (typically 0.9mg/kg) tPA. Our data suggests TNK at a dose of 0.25mg/kg is as effective as tPA dosed at 0.9mg/kg for treatment of AIS, without major safety risks. Furthermore, we saw how TNK could lead to a higher rate of recanalization in patients suffering from large vessel occlusion that might subsequently improve functional outcome. Although more evidence from large-scale RCTs is required to support this hypothesis.