Aim. To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and stages I-III chronic kidney disease (CKD). Subjects and methods. The cohort parallel-group study included 92 patients with AF and stages I-III diabetic and non-diabetic CKD, who were treated with DOACs (dabigatran, rivaroxaban, or apixaban) and vitamin K antagonists (warfarin). The follow-up duration was 12 months. Results. Thromboembolic events and bleeding, which required patient hospitalization or blood transfusions, were not recorded during 1-year follow-up. There was no clinically significant progression of CKD in the groups of therapy with vitamin K antagonists or DOACs. Just the same, a more intense decrease in glomerular filtration rate and a high rate of hemorrhagic complications were revealed in the subgroup of patients with diabetes mellitus (DM) versus those with non-diabetic CKD. Conclusion. In patients with non-valvular AF and diabetic and non-diabetic CKD, the use of DOACs effectively and safely prevents thromboembolic events, irrespective of the stage of CKD. At the same time, in patients taking anticoagulants, CKD progresses more rapidly in the presence of DM than in its absence, regardless of a specific anticoagulant. Hemorrhagic complications are more common in patients with AF, DM, and CKD, which requires more frequent monitoring of their kidney function.