Coronavirus disease 2019 (COVID-19) exists as a pandemic. Mortality during hospitalization is multifactorial, and there is urgent need for a risk stratification model to predict in-hospital death among COVID-19 patients. Here we aimed to construct a risk score system for early identification of COVID-19 patients at high probability of dying during in-hospital treatment.In this retrospective analysis, a total of 821 confirmed COVID-19 patients from 3 centers were assigned to developmental (n = 411, between January 14, 2020 and February 11, 2020) and validation (n = 410, between February 14, 2020 and March 13, 2020) groups. Based on demographic, symptomatic, and laboratory variables, a new Coronavirus estimation global (CORE-G) score for prediction of in-hospital death was established from the developmental group, and its performance was then evaluated in the validation group.The CORE-G score consisted of 18 variables (5 demographics, 2 symptoms, and 11 laboratory measurements) with a sum of 69.5 points. Goodness-of-fit tests indicated that the model performed well in the developmental group (H = 3.210, P = 0.880), and it was well validated in the validation group (H = 6.948, P = 0.542). The areas under the receiver operating characteristic curves were 0.955 in the developmental group (sensitivity, 94.1%; specificity, 83.4%) and 0.937 in the validation group (sensitivity, 87.2%; specificity, 84.2%). The mortality rate was not significantly different between the developmental (n = 85,20.7%) and validation (n = 94, 22.9%, P = 0.608) groups.The CORE-G score provides an estimate of the risk of in-hospital death. This is the first step toward the clinical use of the CORE-G score for predicting outcome in COVID-19 patients.Copyright © 2022 The Chinese Medical Association, published by Wolters Kluwer Health, Inc.