Our objective was to identify the outcome of patients treated with tissue plasminogen activator (r-tPa) in Pakistan and compare these data to available regional and international data. The charts of all patients treated with r-tPa for acute stroke at two centers in Pakistan (Aga Khan University, Karachi and Liaquat National hospital, Karachi) were retrospectively reviewed. We identified 21 patients. The utilization of tPa at Aga Khan Hospital was 18/1,185 patients (1.5%) from 2005 to 2007 while at Liaquat National Hospital was 3/575 patients (0.52%) over 1 year (2007). Mean time interval between stroke onset and start of r-tPa infusion was 169 min. Three patients (14%) developed fatal hemorrhage and two (10%) developed non-fatal hemorrhage. Four patients (19%) died. We identified protocol violations in seven patients (33%). In conclusion, the utilization of thrombolytic therapy is low and complication rate is high. Interventions for training physicians are needed.