Objective To investigate the clinical features of single-vessel disease in female patients with premature coronary heart disease. Methods A retrospective analysis was performed for the female patients, aged <65 years, who were diagnosed with premature coronary heart disease in Jiangyou People’s Hospital from January 2017 to December 2019, and according to the results of coronary CT/coronary angiography, they were divided into single-vessel disease group and multi-vessel disease group. The two groups were compared in terms of baseline data, main hematological indicators, echocardiographic indicators, and comorbidities to explore the clinical features of single-vessel coronary artery lesions in female patients with premature coronary heart disease. Results A total of 368 patients were enrolled, with 144 patients （39.1%) in the single-vessel disease group and 224 patients （60.9%) in the multi-vessel disease group. Compared with the multi-vessel disease group, the single-vessel disease group had a significantly younger age （P<0.05), a significantly lower proportion of patients with a smoking history （P<0.05), and a significantly lower level of high-density lipoprotein cholesterol （P<0.05). Compared with the multi-vessel disease group, the single-vessel disease group had a significantly higher proportion of patients diagnosed with stable angina and a significantly lower proportion of patients with unstable angina or myocardial infarction （P<0.05), as well as a significantly higher left ventricular ejection fraction （P<0.05). Conclusion Female patients with premature coronary heart disease tend to have a younger age of onset of single-vessel disease, with a lower proportion of smokers and a higher ejection fraction, and most patients have stable angina, suggesting that patients with single-vessel disease tend to have a better prognosis.