Objective To analyze the clinical characteristics of antimitochondrial antibody (AMA)-associated cardiac injury. Methods AMA positive patients admitted to West China Hospital of Sichuan University between June 2008 and November 2023 were retrospectively selected. They were categorized into the simple cardiac involvement group and the cardiac and skeletal muscle involvement group according to the presence of skeletal muscle injury. Differences in demographic characteristics, serologic indices, cardiac structure and function, and arrhythmias were compared between the two groups. Results A total of 55 AMA-M2 positive patients with myocardial injury were enrolled. There were 18 cases in the simple cardiac involvement group and 37 cases in the cardiac and skeletal muscle involvement group among them. The age (P=0.002) and mortality rate (P=0.031) of the simple cardiac involvement group were higher than those of the cardiac and skeletal muscle involvement group. There were significant differences in biochemical indicators such as lactate dehydrogenase and α-hydroxybutyrate dehydrogenase between the two groups, and the levels of myocardial enzymes such as creatine kinase isoenzyme, myoglobin and troponin T in the cardiac involvement group were lower than those in the cardiac with skeletal muscle involvement group (P<0.05). Meanwhile, there were significant differences in the incidence of atrial premature beats, atrial fibrillation and other arrhythmias between the two groups (P<0.05). In terms of treatment modalities, glucocorticoids and immunosuppressants were used more frequently in the cardiac combined skeletal muscle involvement group than in the cardiac involvement alone group, whereas β-blockers and diuretics were more prevalent in the cardiac involvement alone group (P<0.05). Conclusion Patients with cardiac involvement alone may have a more insidious or rapid progression of the disease, which requires clinicians to pay higher attention to and provide timely and effective treatment, thus improving the overall prognosis and quality of life of the patients.