Aims <p>China’s primary care was required to improve the quality of atrial fibrillation (AF) management by government. The aim of the study was to investigate whether a clinical decision support system for non-valvular AF (GP-CDSS-2.0) affected appropriate anticoagulation of patients with AF in primary care.</p> Methods and results <p>The study was a cluster randomized controlled study, carried out in 13 community health centers in Shanghai, China, as 1 community health center in the intervention group withdraw the study. Patients with AF who consented to take part in and finish the follow-up were enrolled. We allocated the 14 community health centers into the intervention and control groups using stratified randomization method at a ratio of 1 to 1. General practitioners in the intervention group treated patients using GP-CDSS-2.0, while those in the control group provided usual care. The proportion of appropriate anticoagulation was the primary outcome. The secondary outcomes and safety outcomes mainly included the transition rate of patients’ anticoagulation therapies and the incidences of bleeding and composite adverse outcomes. 405 patients were included in the analyses of primary outcome, with 182 in the intervention group and 223 in the control group. After 1 year’s follow-up, the proportion of appropriate anticoagulation in the intervention group was higher than that in the control group (55.2% in the intervention group and 35.9% in the control group; relative risk (RR) = 1.441, 95% CI, 1.429–1.453, <i>p</i> &lt; 0.001). The proportion of appropriate anticoagulation in the intervention group and the control group increased by 20% and 0.9%, respectively, compared with those at baseline (35.2% in the intervention group and 35.0% in the control group). More subjects in the intervention group experienced a correct transition of their anticoagulation therapies during the study (RR = 2.528, 95% CI, 1.276–5.008, <i>p</i> = 0.008). The intervention group showed a tendency of less bleeding and composite adverse outcomes.</p> Conclusions <p>The utilization of GP-CDSS-2.0 in primary care had the potential to raise the proportion of appropriate anticoagulation among patients with AF. Additionally, it could assist them in transitioning to proper anticoagulation treatments.</p> Trial registration <p>Registration Number ChiCTR2100052307. Registration Date 22/11/2021.</p>