Objective To investigate the risk factors for early neurological deterioration (END) after intravenous thrombolysis within 6 hours after onset in patients with acute ischemic stroke. Methods A retrospective analysis was performed for the clinical data of 151 patients with acute ischemic stroke who were treated with intravenous thrombolysis within 6 hours after onset in our department from July 2017 to August 2019. END was defined as an increase of ≥ 4 points in National Institute of Health Stroke Scale (NIHSS) within 24 hours after thrombolysis, and according to such criteria, the patients were divided into deterioration group and non-deterioration group. The multivariate logistic regression analysis was used to identify the risk factors for END after thrombolysis. Results Of all 151 patients, there were 26 in the deterioration group and 125 in the non-deterioration group. Compared with the non-deterioration group, the deterioration group had significantly higher age, NIHSS score, and prevalence rate of atrial fibrillation (P<0.05) and a significantly shorter onset-to-treatment time (P<0.05), and there was also a significant difference in TOAST typing between the two groups (P<0.05). The logistic regression analysis showed that NIHSS score (odds ratio[OR]=1.124, 95% confidence interval[CI]:1.007-1.254, P<0.05), atrial fibrillation (OR=6.425, 95% CI:1.230-33.561, P<0.05), systolic pressure (OR=1.031, 95% CI:1.001-1.063, P<0.05), and coronary heart disease (OR=0.072, 95% CI:0.006-0.904, P<0.05) were significantly associated with END after intravenous thrombolysis. Conclusions Patients with high NIHSS score, atrial fibrillation, and high systolic blood pressure have a high risk of END after intravenous thrombolysis.