Sex disparities in the management and outcomes of acute coronary syndrome (ACS) have received increasing attention. To evaluate the association of a quality improvement program with sex disparities among patients with ACS. The National Chest Pain Centers Program (NCPCP) is an ongoing nationwide program for the improvement of quality of care in patients with ACS in China, with CPC accreditation as a core intervention. In this longitudinal analysis of annual (January 1, 2016, to December 31, 2020) cross-sectional data of 1 095 899 patients with ACS, the association of the NCPCP with sex-related disparities in the care of these patients was evaluated using generalized linear mixed models and interaction analysis. The robustness of the results was assessed by sensitivity analyses with inverse probability of treatment weighting. Data were analyzed from September 1, 2021, to June 30, 2022. Hospital participation in the NCPCP. Differences in treatment and outcomes between men and women with ACS. Prehospital indicators included time from onset to first medical contact (onset-FMC), time from onset to calling an emergency medical service (onset-EMS), and length of hospital stay without receiving a percutaneous coronary intervention (non-PCI). In-hospital quality indicators included non-PCI, use of statin at arrival, discharge with statin, discharge with dual antiplatelet therapy, direct PCI for ST-segment elevation myocardial infarction (STEMI), PCI for higher-risk non-ST-segment elevation ACS, time from door to catheterization activation, and time from door to balloon. Patient outcome indicators included in-hospital mortality and in-hospital new-onset heart failure. Data for 1 095 899 patients with ACS (346 638 women [31.6%] and 749 261 men [68.4%]; mean [SD] age, 63.9 [12.4] years) from 989 hospitals were collected. Women had longer times for onset-FMC and onset-EMS; lower rates of PCI, statin use at arrival, and discharge with medication; longer in-hospital delays; and higher rates of in-hospital heart failure and mortality. The NCPCP was associated with less onset-FMC time, more direct PCI rate for STEMI, lower rate of in-hospital heart failure, more drug use, and fewer in-hospital delays for both men and women with ACS. Sex-related differences in the onset-FMC time (β = -0.03 [95% CI, -0.04 to -0.01), rate of direct PCI for STEMI (odds ratio, 1.11 [95% CI, 1.06-1.17]), time from hospital door to balloon (β = -1.38 [95% CI, -2.74 to -0.001]), and rate of in-hospital heart failure (odds ratio, 0.90 [95% CI, 0.86-0.94]) were significantly less after accreditation. In this longitudinal cross-sectional study of patients with ACS from hospitals participating in the NCPCP in China, sex-related disparities in management and outcomes were smaller in some aspects by regionalization between prehospital emergency and in-hospital treatment systems and standardized treatment procedures. The NCPCP should emphasize sex disparities to cardiologists; highlight compliance with clinical guidelines, particularly for female patients; and include the reduction of sex disparities as a performance appraisal indicator.