Abstract Background Recent evidence demonstrated an increasing trend for acute myocardial infarction (MI) incidence in young females globally. Identification of distinct clinical comorbidity patterns in this population may allow more precise therapy and improvement in clinical care. Purpose This study was designed to identify specific comorbidity patterns and to examine their associations with in-hospital outcomes in female ST-Segment Elevation Myocardial Infarction (STEMI) patients under 55 years of age based on the China Chest Pain Center (CCPC) Database. Methods From March 7, 2017, to December 29, a total of 267,405 STEMI patients (66,568 females, 24.9%) were admitted to CCPC. Comorbidity patterns were derived among 6,024 female patients (48.5±5.6 years old) under 55 years of age, using hierarchical clustering applied to 15 medical conditions/histories. The study outcome was defined as the composite of in-hospital adverse events (death, new-onset/worsening heart failure, mechanical complications, recurrent MI, and cerebral ischemic stroke). Associations between multimorbidity patterns and clinical outcomes were evaluated by multivariable-adjusted logistic regression models. Results Three comorbidity patterns were derived based on hierarchical clustering, including P1 (histories of hypertension, cerebrovascular disease, heart failure and coronary artery disease), P2 (histories peripheral arterial disease, atrial fibrillation, thyroid dysfunction, anemia, chronic kidney disease, cerebrovascular disease and peptic ulcer) and P3 (obesity, histories of hyperlipidemia, diabetes and smoking, family history of cardiovascular diseases). After adjustment for age, admission levels of systolic blood pressure and heart rate, receiving reperfusion treatment or not, and medical therapies in-hospital (antiplatelet drugs, statins, β-blockers and anticoagulants), compared with participants without multimorbidity, P1 (odds ratios [OR] = 1.60, 95% confidence interval [CI]: 1.26 to 2.04) and P3 (OR = 1.45, 95% CI: 1.10 to1.92) demonstrated relatively higher risks for in-hospital composite outcomes. Compared with patients without comorbidity patterns, the clustering of the above comorbidity patterns dose-dependently augmented the risks for in-hospital composite outcomes, from any one pattern (OR = 1.49, 95% CI: 1.23 to1.81), to any two patterns (OR = 2.46, 95% CI: 1.82 to 3.34) and to three patterns (OR = 4.51, 95% CI: 1.12 to 18.16). Conclusion In a nationwide STEMI registry, our results provided the proof-of-concept evidence that specific comorbidity patterns of young female STEMI were associated with differential in-hospital outcomes. Further work is needed to validate the utility and values in decision making of these multimorbidity patterns for appropriate management strategies in young female STEMI patients. Funding Acknowledgement Type of funding sources: None.