Background and Aims: The Neutrophil-to-Lymphocyte Ratio (NLR) is suggested as a readily available and inexpensive biomarker to predict prognosis of acute stroke. Experience with intravenous (IV) tissue plasminogen activator (tPA) treatment is limited. Methods: Total 142 (80 female, age: 69 +/- 13 yearr) consecutive acute stroke patients treated with IV tPA were evaluated. Admission and 24th hour lymphocyte, neutrophil, and monocyte counts were measured and the NLR was calculated. Results: Average NLR elevated (by 3.47 +/- 6.75) significantly from admission to 24th hour (P < .001). Total 52% of patients exerted good response to IV tPA (NIHSS <= 1 or decrease in NIHSS >= 4 at end of 24 hour), while 27% showed dramatic response (decrease in NIHSS >= 8 at end of 24 hour). The patients with "thrombolysis resistance" had significantly higher 24 hour Neutrophil-to-Lymphocyte Ratio (24h NLR) (P = .001). At the end of 3rd month, 46.5% of patients had favorable (modified Rankin's score, mRS 0-2) and 32.4% had excellent (mRS 0-1) outcome. Patients without favorable/excellent outcome had significantly higher 24h NLRs. Regression analysis indicated that post-tPA, but not admission NLR, was an independent negative predictor of excellent (beta = -.216, P = .006) and favorable (beta = -.179, P = .034) outcome after adjustment for age, hypertension, and admission NIHSS. Nine patients who developed symptomatic intracerebral hemorrhage had elevated pre-tPA (7.6 +/- 7.39 versus 3.33 +/- 3.07, P < .001) and 24h NLR (26.2 +/- 18.6 versus 5.78 +/- 4.47, P < .001). Of note, receiver operating characteristics analysis failed to detect any reliable NLR threshold for absence of tPA effectiveness/dramatic response, 3rd month good/excellent outcome or any type tPA-induced hemorrhage. Conclusions: As a marker of stroke-associated acute stress response, the NLR, which increases during the first 24 hours, is an epiphenomenon of poor prognosis. However, pretreatment NLR values have no importance in predicting IV tPA response.