Abstract Body: Introduction: Coronary artery disease remains the leading cause of mortality globally, and current diagnostic methods rely heavily on invasive coronary angiography. Circulating microRNAs have emerged as promising non-invasive biomarkers, yet their diagnostic accuracy has not been comprehensively updated.

Hypothesis: We hypothesized that circulating miRNA panels achieve superior diagnostic accuracy for CAD compared to single miRNA biomarkers.

Aim: To conduct an updated systematic review and meta-analysis evaluating the diagnostic accuracy of circulating miRNAs for angiography-confirmed CAD.

Methods: We searched PubMed, Embase, and Scopus for diagnostic accuracy studies through December 2025 (PROSPERO: CRD420261279673), supplemented by studies from the prior Fang et al. (2020) meta-analysis. Pooled sensitivity, specificity, and AUC were estimated using bivariate random-effects models. Risk of bias was assessed using QUADAS-2.

Results: Twenty-eight studies (5,374 participants; 34 comparisons) were included. Pooled sensitivity was 0.761 (95% CI: 0.726-0.793) and specificity was 0.767 (95% CI: 0.725-0.805), with AUC of 0.828. Multi-miRNA panels demonstrated superior accuracy versus single miRNAs (AUC 0.912 vs 0.810; DOR 30.72 vs 9.02). Substantial heterogeneity was observed (I²=77.6% sensitivity, 74.0% specificity). Eighty-four percent of studies had high risk of bias due to case-control designs. No publication bias was detected (Deeks' test p=0.865).

Conclusion: Circulating miRNAs demonstrate moderate diagnostic accuracy for CAD, with multi-marker panels showing substantially improved performance. Prospective validation in consecutive patient cohorts with standardized protocols is needed before clinical implementation.