BACKGROUND AND PURPOSE-: Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous tissue-type plasminogen activator-treated patients. METHODS-: Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined as the presence of ≥2 of the following: body temperature <36 C or >38 C, heart rate >90, respiratory rate >20, and white blood cells <4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded. RESULTS-: Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre-tissue-type plasminogen activator National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.16-5.73; P=0.0197). CONCLUSIONS-: In our sample of tissue-type plasminogen activator-treated (tPA) patients, ~1 in 5 patients developed SIRS. Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay. © 2013 American Heart Association, Inc.