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Previous studies reported regional variations in in-hospital acute coronary syndrome (ACS) mortality, but the reasons for that were not clearly defined. We explored whether differences in patient characteristics could explain regional variation. The Improving Care for Cardiovascular Disease in China (CCC)-ACS project is an ongoing national registry and quality improvement project, involving 150 tertiary hospitals from 30 provinces across China. We applied a prediction model that included patient-specific variables to calculate the expected in-hospital mortality. For each province, we reported the observed, expected in-hospital mortality and the risk-adjusted ratio which is based on the observed divided by the expected mortality. From 2014 to 2018, 79 585 ACS patients were enrolled. The average in-hospital mortality was 1.8%. There was a wide variation in the in-hospital mortality among different provinces (0.2-3.9%). Patient characteristics explained part of this variation because of differences in the expected in-hospital mortality (0.7-2.8%). There was a substantial variation in the risk-adjusted ratio among provinces (0.2-3.5), which suggests that the variations in the mortality cannot be completely explained by the differences in patient characteristics. In conclusion, we observed a wide regional variation in mortality for ACS, part of which could be explained by the difference in patient characteristics. [ABSTRACT FROM AUTHOR]