Acute stroke patients can be transferred directly to a Comprehensive Stroke Center (CSC), where acute stroke expertise is provided 24 h a day, seven days a week, and thrombolytic treatment is administered; or they may initially receive attention at an unspecialized community hospital with secondary transfer to the CSC. Our aim is to analyze the influence of previous attention at unspecialized community hospitals on the outcome of ischemic stroke patients treated with thrombolysis. We studied 153 consecutive ischemic stroke patients treated with t-PA over a 30-month period. The primary outcome variable was functional independence at 90 days (Rankin scale, mRS </= 2). Secondary outcomes were neurologic improvement at 24 h, rate of arterial recanalization and symptomatic intracerebral hemorrhage. Forty-five patients (29.5%) received initial attention at community hospitals with secondary transfer to the CSC. Median time from onset to t-PA administration was shorter in patients with direct access to the CSC (135 vs. 165 min; p < 0.001) and stroke severity was higher (NIHSS 12 vs. 9; p = 0.017). Patients who received initial attention at the CSC had a higher frequency of neurologic improvement (59.3% vs. 37.2%; p = 0.014) and a lower rate of symptomatic hemorrhage (4.7% vs. 14%; p = 0.04). Compared to initial attention at an unspecialized hospital, direct admission to the CSC was associated with an odds ratio of 2.48 (95% CI, 1.04-5.88; p = 0.039) for good outcome after adjustment for stroke severity at baseline and other potential confounders. Direct access to a CSC is associated with shorter onset-to-treatment time and better outcome for ischemic stroke patients treated with thrombolysis in comparison with initial attention at an unspecialized hospital with secondary transfer.