This study aimed to investigate the clinical characteristics and risk factors for the wearing-off (WO) phenomenon of Parkinson’s disease (PD) in female patients. Methods: In this cross-sectional study, we continuously collected the clinical data of female patients who met the PD diagnostic criteria. General demographic and clinical data, including motor symptoms, non-motor symptoms, possible combination with WO, and drug-related factors, were collected. Results: A total of 146 female patients with PD were enrolled and divided into the WO group (n=63 cases, 43.2% ), and the no-WO group (n=83 cases). Compared with the no-WO group, the WO group had an earlier age of onset , lower body weight and BMI, longer disease duration, more severe disease, higher Levodopa Equivalent Daily Dose (LEDD), and a greater risk of complication with depression (all, P<0.05). Multivariate logistic regression analysis revealed that older age at onset (OR=0.923, P= 0.003) was a protective factor for WO in female patients, while longer disease duration (OR=1.256, P=0.003) and higher Hoehn and Yahr (H-Y) stage (OR=2.074, P=0.011) were risk factors for WO. Conclusion: The risk factors of the WO phenomenon in female patients with PD include young age at onset, longer disease duration, and high H-Y stage.