Non-ST-elevation acute coronary syndrome (NSTE-ACS) is a prevalent condition in emergency settings, with lesion severity influencing treatment pathways. The SYNTAX score is determined by coronary angiography, which accurately assesses lesion complexity but is an invasive procedure. In contrast, the HEART score – based on history, electrocardiogram, age, risk factors, and troponin – offers a non-invasive, rapid assessment tool. This study evaluated the effectiveness of the HEART score in predicting the severity of coronary lesions, as represented by the SYNTAX score, in patients with NSTE-ACS. This cross-sectional study included 120 patients with NSTE-ACS admitted to Trung Vuong Hospital between December 2023 and September 2024. Patients were assessed for the HEART score and coronary angiography within 48 h of admission. The SYNTAX scores categorized patients into low- (0 – 22), moderate- (23 – 32), or high-risk groups (≥33). Spearman’s correlation was used to assess the HEART–SYNTAX relationship, with receiver operating characteristic (ROC) analysis identifying the optimal HEART score cutoff for predicting SYNTAX ≥23. The mean age of the cohort was 63.9 years, of which 66.7% were men. Common risk factors included hypertension (80.8%), hyperlipidemia (73.3%), and diabetes (25.8%). A significant positive correlation (ρ = 0.819, P < 0.001) was observed between the HEART and SYNTAX scores, with higher HEART scores reflecting greater lesion complexity than SYNTAX scores. ROC analysis yielded an area under the curve of 0.912 (95% CI: 0.862 – 0.963), with a HEART score cutoff of 5 showing 90.6% sensitivity and 83.9% specificity for predicting moderate-to-high SYNTAX scores (≥23). The HEART score is an effective, non-invasive predictor of coronary lesion complexity in patients with NSTE-ACS, significantly correlating with the SYNTAX scores. A HEART score of ≥5 accurately identifies patients at risk for severe coronary disease, supporting its use in rapid, non-invasive risk stratification and facilitating timely intervention in emergency settings.