Objective To investigate related factors for levodopa-related wearing-off in Parkinson's disease (PD).Methods The clinical data of PD patients were collected, and a statistical analysis was performed to investigate the factors for wearing-off.Results The occurrence of wearing-off was not associated with sex, age, years of education, body weight, a contact history of poisons and drugs, smoking history, drinking history, high-protein diet, and a history of cerebrovascular diseases (all P>0.05). The patients who experienced wearing-off tended to have an earlier age of onset, a longer course of disease, higher initial and terminal doses of levodopa, a longer duration of levodopa medication, a higher H&Y stage, and higher scores of Unified Parkinson's Disease Rating Scale-Ⅲ and Hamilton Anxiety Scale (HAMA) (P<0.05). Age of onset, initial dose of levodopa, H&Y stage, and anxiety were independent influencing factors for wearing-off (P<0.05), and H&Y stage, HAMA score, age of onset, and initial dose of levodopa were independent predictive factors (P<0.05). H&Y stage had good sensitivity and specificity (80.9%). The risk of wearing-off in advanced patients increased over the time of treatment.Conclusions Many factors may influence the development of wearing-off during levodopa treatment.