PURPOSE: We report the Belgian results of the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Register (SITS-ISTR). This prospective observational register evaluates the safety and efficacy of intravenous thrombolysis with rtPA (recombinant tissue Plasminogen Activator) for ischemic stroke in routine clinical practice. METHODS: We compared the baseline characteristics, treatment delay, rate of symptomatic intracerebral hemorrhage and functional outcome at 90 days after treatment between patients enrolled in centres in Belgium and the non-Belgian SITS-registry population. We performed a multivariate analysis to adjust for differences in demographic and baseline characteristics. RESULTS: 743 patients were enrolled in 42 centers in Belgium between December 2002 and December 2007. These patients were older, had more severe stroke were more frequently female and more frequently had hyperlipidemia and atrial fibrillation. The median stroke onset-to-treatment delay was 140 min vs. 145 min. More patients died and were disabled 3 months after the stroke. A slight, non-significant, increase of symptomatic intracerebral hemorrhage (SICH) as per SITS protocol was observed (2.4 vs. 1.6%, p = 0.15). After adjustment for differences in baseline characteristics, functional independence (mRS < or = 2) at 3 months (OR 0.95, 95% CI 0.86-1.05, p = 0.31) was not different from non-Belgian patients, nor was the rate of SICH. However mortality at 3 months in Belgian patients was slightly higher (OR 1.15, 95% CI 1.02-1.29, p = 0.02). CONCLUSION: Intravenous thrombolysis for ischemic stroke is safe and effective in the routine clinical use in Belgium. The higher mortality we observed is not related to a higher rate of SICH.