We report the 5-year experience with thrombolysis in acute ischemic stroke from a tertiary care hospital in the Malabar region of South India. All stroke patients thrombolyzed with intravenous recombinant tissue plasminogen activator (rt-PA) from May 2003 to May 2008 were studied in an open, non-randomized, prospective study. Of 2,308 ischemic stroke patients admitted, 57 patients (2.5%) were thrombolyzed with rt-PA (age range, 35-78 years: 40 males, 17 females). The time from presentation at the hospital to initiation of thrombolysis ranged from 15 to 120 minutes (median 50 minutes). The dose of rt-PA used was from 0.6 mg/kg to 0.9 mg/kg. At 3 months 29 patients (51%) were functionally independent, with a modified Rankin scale score of 2 or less. Seven patients (12%) died within 3 months; one had an intracerebral hemorrhage (1.7%). The benefit of treatment was seen in all stroke subtypes. We have been able to show that intravenous thrombolysis in acute ischemic stroke is safe, effective and feasible in our part of the world.