Thrombolysis has not been fully implemented into clinical practice in the developing world primarily due to economic restraints. The study assessed the cost-effectiveness (CE) and estimated annual savings of thrombolysis with recombinant tissue plasminogen activator (rt-PA, alteplase) within 4.5 hours after acute ischemic stroke (AIS) versus standard care from the Mexican Institute of Social Security (IMSS) perspective. Standard care (SC) was defined as inpatient treatment of the AIS without utilization of thrombolytic agents. A decision-analytic model was developed. Efficacy, direct costs and resources were obtained from IMSS available data and published studies. Effectiveness outcomes included the percentage of patients who responded favorably to treatment (no disability and able to carry out all usual activities) between the time of diagnosis + 1 year (time horizon). Additionally analyses evaluated cost savings in patients with AIS (> 80 years old) who responded favorably to the treatment. Discount rates were not applied to the model. A sensitivity analysis was conducted to evaluate the impact of the uncertainty variables. The estimated total cost per patient was $23,53.20 for SC and $23,663.93 for rt-PA. The percentage of patients who responded favorably to treatment was 16% in the rt-PA and 12% in SC. The CER were USD $193,241.02 for SC and USD$146,924.34 for rt-PA. This equated to a cost-savings of $46,316.67/percentage of patients recovered with no symptoms/disabilities. The projected savings over a five-year period (2013-2017) in the IMSS ranged from $9,626,458 and $22,015,454. The results from the analyses indicated that rt-PA provided a highly cost-effective and saving alternative compared with SC. In medical settings where thrombolysis is not yet a common practice, rt-PA is a cost effective treatment to improve functional outcome in patients treated promptly after acute ischemic stroke.