The aim of this study was to investigate the outcomes of human urinary kallidinogenase (HUK) after recombinant tissue-type plasminogen activator treatment in patients with acute ischemic stroke (AIS).In this retrospective study conducted from December 2018 to August 2020, 313 patients with AIS patients who received recombinant tissue-type plasminogen activator treatment were enrolled. Among them, 148 patients received basic therapy, and 165 patients received HUK treatment. Demographics and clinical characteristics were analyzed after treatment, and patients were monitored for stroke recurrence for 12 months. National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale scores were used to assess the efficacy of treatment. Logistic regression analysis was used to identify risk factors for recurrence.There were no differences in baseline clinical characteristics between the 2 groups in the database. After 14 days of treatment, the HUK group had significantly lower NIHSS and modified Rankin Scale scores than the control group (P<0.01). The recurrence rates in the HUK and control groups were 12.84% and 21.82%, respectively, with patients treated with HUK having better outcomes (P<0.001). Logistic analysis indicated that high homocysteine levels and high NIHSS scores at diagnosis were risk factors for AIS recurrence. In addition, HUK treatment was found to reduce the risk of recurrence.Treatment with HUK after intravenous thrombolysis can significantly improve the neurological function of AIS patients and reduce stroke recurrence.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.