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Background: Both atrial cardiopathy and impaired renal function are independently associated with increased mortality, but their interrelationship and combined impact remain uncertain. Methods: We analyzed 6573 participants from NHANES-III (mean age 57 years; 50.5% women; 74.6% White) with available electrocardiograms (ECGs). Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Atrial cardiopathy was defined by any of the following ECG markers: abnormal P-wave axis (<0° or >75°), deep terminal negativity in lead V1 (>100 µV), or prolonged P-wave duration in lead II (>120 ms). Participants with eGFR <15 mL/min/1.73 m² or major ECG abnormalities were excluded. Logistic regression assessed the association between impaired renal function (eGFR < 45 vs. ≥45 mL/min/1.73 m²) and atrial cardiopathy. Cox models evaluated independent and joint associations of impaired renal function and atrial cardiopathy with all-cause mortality. Results: About 47.9% (n = 3151) had atrial cardiopathy at baseline, of whom 161 (4.7%) had impaired renal function. Impaired renal function was associated with higher odds of atrial cardiopathy (OR 1.44; 95% CI 1.16–1.78). Over a median follow-up of 18.1 years, 3076 deaths occurred. Compared with participants without either condition, those with both had the highest mortality risk (HR 1.68; 95% CI 1.46–1.94), exceeding risks from atrial cardiopathy alone (HR 1.10; 95% CI 1.02–1.18) or impaired renal function alone (HR 1.42; 95% CI 1.18–1.70; p = 0.011 for interaction). Conclusions: Impaired renal function is associated with a greater prevalence of atrial cardiopathy. Their coexistence exerts a synergistic effect, substantially amplifying mortality risk beyond either condition alone. Full article