Aim. To evaluate the clinical and prognostic significance of atrial functional mitral regurgitation (AFMR) in patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) on the background of optimal drug therapy. Materials and methods. The retrospective study included 150 patients (age 75.5±9.9 years, 54% men) with HFpEF with AF and AFMR on the background of optimal drug therapy. Clinical and demographic characteristics (including the scale of assessment of the clinical condition), laboratory and instrumental diagnostic results, and drug therapy were evaluated. MR was assessed as minor, moderate, or severe using a multiparametric approach, including an assessment of the effective area of the regurgitation hole and the MR fraction. The effect of AFMR on rehospitalization for HF, combined endpoint (CE) was studied [cardiovascular death (CVD) and rehospitalization] during the follow-up period of 589 (217–1039) days. Results. Eighty (53.3%) patients had moderate AFMR, and 23 (15.3%) had severe AFMR. These patients had lower SBP and DBP values (p=0.014), and permanent AF was more common among them (p=0.025) compared with patients with minor MR. Independent predictors of moderate/severe AFMR were the constant form of AF (OR 3.3 [1.4–8.0]; p=0.007), end-systolic left ventricular distance (OR 3.0 [1.4–6.5]; p=0.006), taking antiplatelet agents (OR 0.11 [0.02–0.70]; p=0.020). The frequency of outcomes in the general group was 46.7% for CE, 34.0% for rehospitalization for HF, and 14.0% for CVD. The predictors of CE were moderate/severe FMR (HR 2.6 [1.4–4.9]; p=0.002), scores on the scale of assessment of the clinical condition (HR 1.14 [1.04–1.25]; p=0.003); severe FMR (HR 4.1 [1.7–10.2]; p=0.002), moderate FMR (HR 2.7 [1.2–5.8]; p=0.013), creatinine level (HR 0.990 [0.980–1,000]; p=0.040). Conclusion. Despite the limitations, the importance of AFMR as a factor influencing clinical outcomes in patients with HFpEF and AF has been demonstrated. The present study highlights the need for further investigation of this condition and the development of personalized patient management strategies. © 2025 Elsevier B.V., All rights reserved.