Background: Spontaneous reperfusion (SR) and early infarct related artery (IRA) patency before primary percutaneous coronary intervention (PPCI) might bring extra benefit for patients with ST-segment elevation myocardial infarction (STEMI). This study premilinarily screened the independent predictors of SR, and assessed the relationship between SR and plasma homocysteine (HCY). Methods: The medical records of 998 patients who were diagnosed as STEMI and underwent emergency coronary angiography were retrospectively studied, SR was defined as achievement of TIMI grade 3 flow in the IRA before PCI. The baseline characteristics, clinical manifestations and hematological variables were compared between SR and NSR group. Optimal cutoff point of HCY was calculated with receiving operating characteristics (ROC) analysis, multivariate logistic regression models were used to identify predictors of SR. Results: 229 (22.95%) patients showed angiographic SR. For HCY, the area under the curve was 0.70 (95% CI: 0.63-0.77, P = 0.034), the optimized cut off point was 17.55 mu mol/L. Preinfarct angina (95% CI: 1.61-5.65, P = 0.0005), plasma C-reactive protein (CRP) level (95% CI: 0.87-0.99, P = 0.016) and HCY < 1755 mu mol/L (95% CI: 2.43-8.72, P < 0.0001) were found to be independent predictors for SR. Conclusion: In patients with STEMI, HCY < 17.55 mu mol/L, preinfarct angina and plasma CRP level were independent predictors of SR.