Background: More than 70% of strokes occur in resource-poor countries. Outcomes are often not well documented. rt-PA for acute ischemic stroke was approved in 2012 for use in Costa Rica (CR). A hub and spoke model was initiated and a dataset established, the CR Stroke Registry Program (CRSRP) for conditional- and post-approval monitoring. Here, we compared CRSRP rt-PA outcomes to similarly treated subjects from the 1995 NINDS rt-PA trial and the 2019 CLOTBUST-ER control arm. Methods: Subjects were matched using a published pairing methodology and day 7-10/discharge modified Rankin Score (mRS), symptomatic intracerebral hemorrhages (SICH) and early mortality compared. A mortality model was generated from 15 randomized controlled trials (RCTs) and outcomes compared at similar baselines. SICH rates were compared with other cohorts: Get With The Guidelines (GWTG), a combined international IV thrombolysis trial pool, and 2 Ibero-American populations. Results: Of 424 CRSRP patients, 284 receiving rt-PA under 3 hrs were matched with 308 NINDS subjects. 131 non-diabetic CRSRP subjects, treated within 4.5 hrs, NIHSS 10 - 24 and Alberta Stroke Program Early CT Score (ASPECTS)>7, were matched with 300 CLOTBUST-ER subjects. Percent achieving either mRS 0-1 or 0-2 did not differ between CRSRP and either NINDS or CLOTBUST-ER (mRS 0-1: CRSRP:33.9% vs NINDS:33.6%; CRSRP:23.8% vs CLOTBUST-ER:27.0%, all p>=.05 / mRS 0-2: CRSRP:40.0% vs NINDS:41.4%; CRSRP:31.1% vs CLOTBUST-ER:36.1%, all p=>.05). Mortality was higher for CRSRP vs CLOTBUST-ER (6.6% vs 0.8%; p=0.05) but not vs NINDS (6.8% vs 4.3%; p=0.3). A predictive model (R 2 =0.39) showed neither cohort exceeded expected pooled mortality, with CLOTBUST-ER the lowest mortality. SICH rate was higher in CRSRP vs CLOTBUST-ER (7.3% vs 0.0% p=0.008) but not vs NINDS (5.7% vs 6.8% p=0.7)). SICH rates were not higher when compared with 4 international cohorts. Conclusion: Functional outcomes of Costa Rican patients receiving rt-PA compared favorably with 2 RCTs (NINDS and CLOTBUST-ER). SICH and mortality were higher than CLOTBUST-ER, although both were within expected range compared to other international cohorts. Systems of care development in order to further lower SICH and participate in the endovascular era are underway.