Objective To investigate the relationship between the early neutrophil-to-lymphocyte ratio (NLR) in peripheral blood, poor prognosis and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis treatment. Methods The retrospective study included 221 AIS patients who underwent intravenous thrombolysis therapy. Demographic information, medical history, clinical and imaging data were collected. Peripheral venous blood samples were drawn before treatment for routine blood tests, and NLR was calculated. The primary endpoint was poor prognosis or death at 3 months after onset, and the secondary endpoint was symptomatic intracranial hemorrhage (SICH) or END within 24 hours after thrombolysis. Logistic regression was used to analyze factors associated with the primary and secondary endpoint events. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of NLR for clinical outcomes. Results Logistic regression analysis revealed that female, hypertension, higher baseline NLR (OR=1.968, 95%CI: 1.516-2.555, P<0.001) and NIHSS scores were independent risk factors for 3-month poor outcomes in AIS patients. Female, a history of stroke or transient ischemic attack (TIA), higher random blood glucose, elevated baseline NLR (OR=1.317, 95%CI: 1.028-1.688, P=0.030) and NIHSS scores were independent risk factors for 3-month mortality. Hypertension, elevated homocysteine, higher baseline NLR (OR=1.420, 95%CI: 1.180-1.709, P<0.001) and NIHSS scores were independent risk factors for END. There was no significant difference in NLR level between the SICH group (n=5) and the non-SICH group (n=216). ROC curve analysis showed that baseline NLR had high predictive value for 3-month poor outcomes, 3-month mortality and END in AIS patients, with AUCs of 0.748 (95%CI: 0.679-0.817), 0.738 (95%CI: 0.622-0.853) and 0.730 (95%CI: 0.656-0.804), respectively. There was no predictive value for SICH. Patients in the high NLR group (NLR≥2.63, n=89) had significantly higher baseline NIHSS scores, random blood glucose levels and rates of hypertension, coronary artery disease, END, 3-month poor outcomes and 3-month mortality compared to those in the low NLR group (NLR<2.63, n=132). Conclusion Elevated baseline NLR is associated with the occurrence of END and 3-month poor outcomes in AIS patients following intravenous thrombolysis therapy, suggesting its potential as a biomarker for predicting clinical outcomes in AIS patients.