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• High NLR value predicts poor response to intravenous rt-PA in Caucasian stroke patients. • The predictive value of NLR is observed for both the short-term clinical outcome and the 3-month mortality. • The association between NLR and stroke outcome is likely to be non-linear. • High NLR may increase the usefulness of existing scales for identifying patients with borderline indications for rtPA who are unlikely to benefit from the treatment. Our aim was to investigate usefulness of the neutrophil-to-lymphocyte ratio (NLR) for predicting poor response to intravenous rtPA in white Caucasian ischemic stroke patients treated within 4.5 hours from the onset. This retrospective analysis included all consecutive acute ischemic stroke patients (N = 344) treated with rtPA in a tertiary stroke center from 2011 to 2017. NLR was calculated from complete blood counts obtained on admission. The patients were classified into NLR terciles (T1 <1.75, T2<2.97, T3≥2.97). Significant neurological improvement was defined as an 8-point reduction in the NIHSS score or reaching the score of 0 to 1. Compared to NLR T1, patients from NLR T3 were significantly older, more often disabled before stroke, and had longer onset-to-needle time. They less often achieved neurological improvement at day 7 (38% vs 59% p=0.002) and had higher 90-day mortality (27% vs 13%, p=0.020), with no differences in neurological improvement at 24 hours, occurrence of sICH and 7–day mortality. Each additional 4 units of NLR decreased unadjusted and adjusted odds for achieving favorable outcome at day 7 (OR 0.65, 95% CI: 0.46-0.92; aOR 0.62, 95% CI: 0.39-1.00), and increased the odds for death at 3 months (OR 1.60, 95% CI: 1.15-2.24; aOR 1.82, 95% CI:1.14-2.92) High NLR can predict poor response to intravenous rtPA in Caucasian patients with acute ischemic stroke, especially in terms of not achieving significant neurological improvement at day 7 and death at day 90. It encourages attempts to incorporate NLR in already validated scores. [ABSTRACT FROM AUTHOR]