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Abstract Background Intravenous recombinant tissue plasminogen activator is the only golden approved medical therapy for acute ischemic stroke, guidelines for its injection relay on reducing or preventing associated hemorrhage as a side effect, yet hemorrhage is not the only possible complication, further embolization following injection is also a possibility; in this case report, peripheral embolization following intravenous recombinant tissue plasminogen activator with two possible explanations one related to the treatment and another related to the patient liability is represented. Case presentation A 78-year-old male presenting with acute onset of stroke, received intravenous recombinant tissue plasminogen activator, 16 h later he developed acute limb ischemia. Conclusion Peripheral embolization may happen within hours from intravenous recombinant tissue plasminogen activator administration.