We sought to explore the trends and influencing factors of the use of anticoagulants in patients with acute ischemic stroke and non-valvular atrial fibrillation (NVAF) at discharge in the era of novel oral anticoagulants (NOACs).We recruited consecutive inpatients with acute ischemic stroke and NVAF in a registered study (NCT04080830) from January 2016 to December 2021. The relevant data of patients were collected. We compared the proportions of anticoagulant treatment at discharge before and after NOACs entered China's medical insurance system. The proportion of each antithrombotic status as well as anticoagulant agents at discharge in every year were calculated, and the trends during the study period were analyzed. The relevant factors affecting anticoagulant use at discharge were further analyzed.The proportion of anticoagulation at discharge increased significantly after NOACs entered China's medical insurance system in 2018 versus before (χ2 = 42.828, P < 0.001). There were statistically significant differences in antithrombotic status (χ2 = 69.954, P < 0.001) and in the proportion of different anticoagulant drugs (χ2 = 63.049, P<0.001) by year. Anticoagulant therapy (χ2 = 1.55, P = 0.671) and NOACs (χ2 = .178, P = 0.243) increased over 2016-2018 but was relatively stable during 2018-2021. Multivariate logistic regression analysis showed that age ≥75 years, coexisting cerebral artery stenosis, massive cerebral infarction and hemorrhagic transformation were independent risk factors affecting anticoagulants use (all P < 0.05).NOACs have indeed improved anticoagulants use in patients with acute ischemic stroke and NVAF at discharge. However, some specific factors affect anticoagulation therapy use at discharge and hinder further improvement even in the NOACs era.Copyright © 2022 Elsevier Inc. All rights reserved.