The existing risk sores for ST-elevation myocardial infarction (STEMI) patients cannot balance timeliness, feasibility, and accuracy. This study aimed to develop and validate a two-stage scoring system capable of dynamic evaluation for 30-day mortality among STEMI patients. We recruited 3939 patients and randomly assigned (7:3) to derivation (N = 2757) and internal validation (N = 1182) datasets, an independent cohort of 1315 STEMI patients was used for external validation. The two-stage scoring system was developed based on factors associated with 30-day mortality identified by multivariate analysis and their availability in course of management. The first medical contact (FMC) stage risk score comprised six predictors (age, gender, systolic blood pressure, heart rate, Killip class, and anterior myocardial infarction), the in-hospital risk score included serum creatinine and left ventricular ejection fraction on this basis. The area under the curve (AUC) were 0.816, 0.854, 0.843, and 0.876 in derivation and internal validation for FMC and in-hospital stage risk score with satisfactory calibration ability. FMC stage risk score displayed equivalent predictive ability with TIMI risk score and GRACE score, in-hospital stage risk score obtained promotion in AUC, integrated discrimination improvement, and net reclassification improvement (all P <
0.001) compared with the classic risk scores. The reproducibility and effectiveness of the risk scores were statistically confirmed in the external validation cohort. The two-stage scoring system had good ability for predicting 30-day mortality and useful to dynamically identify high-risk STEMI patients.Trial registration: [NCT02641262] [29 December 2015].