Objective To investigate whether the circadian timing of symptom onset influences the severity of myocardial ischemia-reperfusion injury （MIRI） following primary percutaneous coronary intervention （PCI） in patients with acute ST-segment elevation myocardial infarction （STEMI）. Methods This retrospective study included 362 consecutive STEMI patients who underwent primary PCI within 12 hours of symptom onset at the Affiliated Hospital of Yangzhou University between January 2021 and December 2024. Patients were stratified into four circadian groups based on symptom onset time： nighttime， morning， afternoon， and evening. Primary outcomes included peak creatine kinase-MB （CK-MB） and cardiac troponin I （cTnI） levels. Secondary outcomes encompassed post-PCI TIMI flow grade， incidence of no-reflow phenomenon， left ventricular ejection fraction （LVEF） at 7 days， and major adverse cardiovascular events （MACE） at 7 and 30 days. Group comparisons used Kruskal-Wallis or one-way ANOVA tests as appropriate. Multivariable linear and logistic regression models identified independent associations between circadian timing and myocardial injury markers or no-reflow risk. Results Peak CK-MB and cTnI levels were significantly higher in the nighttime and morning groups compared with the afternoon and evening groups （all P 0.05）. The nighttime group exhibited the highest incidence of no-reflow phenomenon （24.3% vs. 9.7% in the afternoon group， P = 0.018）. LVEF at 7 days was lowest in the nighttime group （51.3 ± 7.8） % and highest in the afternoon group ［（57.2 ± 6.4）%， P = 0.003］. After adjustment for total ischemic time， infarct location， and Killip class， nighttime and morning onset remained independent predictors of elevated peak cTnI. Nighttime onset was independently associated with no-reflow risk. Conclusions The circadian timing of symptom onset is independently associated with MIRI severity following primary PCI for STEMI. Patients with nighttime onset experience greater myocardial necrosis， higher rates of microvascular obstruction， and impaired early ventricular recovery. These findings suggest that circadian biology may modulate ischemia-reperfusion pathophysiology， supporting the integration of symptom onset timing into risk stratification protocols for STEMI management.