Argatroban in acute noncardioembolic stroke ineligible for intravenous thrombolysis (IVT) or endovascular treatment (EVT) remains unclear. This study aimed to evaluate whether argatroban improved early and long-term outcomes compared with antiplatelet treatment. This retrospective observational study, using the prospective stroke database from our hospital, included all consecutive patients who hospitalized from January 1, 2017 to December 31, 2019, with a diagnosis of acute non-cardioembolic stroke within 48 hours of stroke onset but not receiving IVT and EVT. Patients were divided into 2 groups: the argatroban group and the control group without argatroban. Outcome assessment with early neurological deterioration (END), National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), bleeding complications, and mortality were compared between the 2 groups in all cases and different stroke subtypes. An ordinal logistic regression analysis evaluated the association between argatroban use and mRS score at 90 days. Of 1325 patients were enrolled, 519 patients in the argatroban group and 806 in the control. Baseline characteristics, hospital bleeding complications, and 90-day mortality were similar for the 2 groups. The argatroban group showed lower END, larger improvement of 7-day NIHSS score and higher percentage of a 90-day mRS score of 02. Similar results were found in subgroup analysis with large-artery atherosclerosis, anterior circulation infarction, and moderate stroke. Also, argatroban use was significantly associated with an excellent long-term stroke outcome (mRS ≤ 2). The current study suggested that argatroban was safe and effective for improving short and long-term outcomes in noncardioembolic stroke patients. Copyright © 2020 Elsevier B.V. All rights reserved.