Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute coronary syndrome (ACS), and approximately 25% of patients present with acute total occlusion (ATO) of the culprit vessel. ATO may lead to more extensive myocardial injury and poorer outcomes. However, its prognostic significance in NSTEMI, particularly in the Chinese population, is not well established. This study aimed to evaluate the association between the occlusion status of the culprit vessel and clinical outcomes in NSTEMI patients. This retrospective study included 1,128 NSTEMI patients who underwent coronary angiography. Patients were categorized into total occlusion (TO) and non-total occlusion (Non-TO) groups based on the occlusion status of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unplanned revascularization, and rehospitalization for heart failure. ATO was identified in 286 patients (25.4%), most frequently involving the left circumflex artery. Over a median follow-up of 3.6 years, patients in the TO group had a 46% higher risk of MACE compared to those in the Non-TO group (adjusted hazard ratio [aHR]: 1.46; 95% confidence interval [CI]: 1.16-1.83; P = 0.002). Incorporating occlusion status into the GRACE score improved its predictive accuracy for MACE. ATO of the culprit vessel was independently associated with an increased risk of MACE in NSTEMI patients. The occlusion status of the culprit vessel could aid in risk stratification and prognostic assessment in this population.Copyright © 2025. Published by Elsevier Inc.