Background: Oral anticoagulants (OACs) such as warfarin and non-VKA oral anticoagulants (NOACs) have been recommended for patients with atrial fibrillation (AF) who are at risk for stroke. Whether NOACs have a higher persistence than warfarin is still unclear. This is especially true in China. Material/Methods: Data from a large hospital-based cohort in China (China-AF Registry) from 2011 to 2017 were used for this study. Non-valvular AF patients with newly initiated OACs were included. A time-to-event approach was used to analyze patient persistence. The survival distributions of persistence were compared using the log-rank test. A multivariable Cox regression model was used to explore predictors of warfarin and NOACs non-persistence. Results: Patients with newly initiated warfarin (n=4845) or NOACs (n=854) were included in this study. Persistence rates at 1, 2, and 3 years were 93.2%, 89.4%, and 87.2% in the warfarin group and 88.8%, 84.3%, and 81.3% in the NOAC group respectively. Non-persistence was significantly higher with NOACs than with warfarin. On multivariate analysis, age <75 years old, outpatient clinic visits, asymptomatic AF, paroxysmal AF, duration of AF <3 years, history of peptic ulcer, and no previous TIA, stroke or thromboembolism were strong predictors of warfarin non-persistence, while in the NOACs group, age <75 years old, outpatient clinic visits, lower education status and no history of congestive heart failure were predictors. Conclusions: Treatment persistence of NOACs was lower than that of warfarin among Chinese patients with AF. Patients with characteristics of non-persistence predictors need special attention to maintain their therapy.