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From 2006, the Stroke Code system operates throughout Catalonia with full coverage. The objective of this study was to determine safety and effectiveness of intravenous thrombolysis in routine practice through a monitored study (Catalan Stroke Code and Thrombolysis [Cat-SCT]) and to assess outcomes according to hospitals' previous experience.We conducted a prospective, multicenter, observational, monitored study of recombinant tissue plasminogen activator-treated patients declared to the Cat-SCT by all treating hospitals in Catalonia (n=13, of which 6 were newly designated) over a 12-month period. Consecutive recruitment and quality of data were assured through comprehensive quality control. We estimated rates of outcome measures for the potential final sample (after inclusion of undeclared cases) and compared them with those reported for the actual sample. Symptomatic intracranial hemorrhage, mortality, and favorable outcome (modified Rankin Scale score 0 to 1) at 3 months were also evaluated according to hospitals' previous experience using multilevel logistic regression.We analyzed 488 patients with a median age of 72 years (interquartile range: 63, 77), 57.2% males, with a baseline National Institutes of Health Stroke Scale score of 13 (interquartile range: 8, 19), and stroke to treatment time of 150 minutes (interquartile range: 120, 180 minutes). Symptomatic intracranial hemorrhage (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy definition) was observed in 3.3% patients. Ninety-day mortality was 16.6% and 38.5% showed a favorable outcome at 3 months. External monitoring set inclusion losses at <5%. A sensitivity analysis including undeclared cases did not show significant changes in main outcomes. Inexperienced hospitals achieved similar outcomes, except for a higher rate of favorable outcome at 3 months.Health planning applied to acute stroke care and based on dissemination of the Stroke Code system and designation of new referral hospitals showed intravenous thrombolysis safe and effective in routine practice, even among inexperienced hospitals.