Objective: To investigate the predictive value of three-dimensional ultrasound combined with neutrophil/lymphocyte ratio (NLR) and D-dimer in elderly patients with non-valvular atrial fibrillation. Methods: From January 2020 to December 2021, 102 elderly patients with non-valvular atrial fibrillation (observation group) and 100 healthy subjects (control group) admitted to our hospital during the same period were selected as the research objects. Cardiac examination, NLR expression level was detected by automatic blood cell analyzer, and D-dimer was detected by enzyme-linked immunosorbent assay. The differences in the detection results of three-dimensional echocardiography, NLR, and D-dimer between the two groups were compared, and the relationship between three-dimensional echocardiography, NLR, D-dimer and poor prognosis of non-valvular atrial fibrillation was analyzed by Logistic regression analysis. Receiver operating characteristic (ROC) curve analysis of three-dimensional echocardiography, NLR, and D-dimer in the prognosis prediction of non-valvular atrial fibrillation. Results: The detection values of LVEDV, LVESV, RVEDV, RVESV, NLR, and D-dimer in the observation group and patients with poor prognosis were significantly higher than those in the control group. Patients with good prognosis, while the detection values of LVEF and RVEF in the observation group and patients with poor prognosis were significantly lower than those in the control group. There was a statistically significant difference between the two groups and those with good prognosis (P<0.05). Logistic regression analysis showed that three-dimensional ultrasound (high expression of LVEDV, LVESV, RVEDV, and RVESV), NLR (high expression), and D-dimer (high expression) were the influencing factors of poor prognosis in non-valvular atrial fibrillation (P<0.05). The results of drawing receiver operating characteristic (ROC) curve showed that the combination of three-dimensional ultrasound, NLR, and D-dimer had the highest AUC (0.855, 95%CI: 0.768~0.942) in predicting the prognosis of non-valvular atrial fibrillation. The sensitivity and specificity were 92.65% and 91.18% respectively (P<0.05). Conclusion: Three-dimensional ultrasound (LVEDV, LVESV, RVEDV, RVESV high expression), NLR (high expression), and D-dimer (high expression) are the influencing factors of poor prognosis in non-valvular atrial fibrillation, which can provide quantitative reference for predicting the prognosis of non-valvular atrial fibrillation.