The objective of this study was to investigate the risk factors of wearing-off 
phenomenon in Parkinson's disease (PD) and propose safe dosage of levodopa to 
reduce wearing-off development based on Chinese cohort. Patients with PD who had 
taken levodopa (L-dopa) for at least 1 month were recruited. Wearing-off was 
diagnosed based on validated Chinese version of a patient self-rated 9-question 
Wearing-Off Questionnaire (WOQ-9) and clinical definition. Eleven variables 
(gender, disease duration at L-dopa initiation, disease duration at assessment, 
age at onset, age at assessment, H-Y stage, UPDRS III, L-dopa daily total dosage 
and dosage adjusted to weight, duration of L-dopa treatment, initial drug 
recipe) were included in our analysis. Univariate analysis, multivariate 
logistic regression analysis and decision tree classification model(DTC) were 
used to detect risk factors of wearing-off. Receiver operating characteristic 
(ROC) curve and DTC were used to investigate cut-off value of L-dopa to best 
predict wearing-off. Two hundred and thirty-four patients were investigated in 
our study, among whom 111 developed wearing-off. Patients with wearing-off 
tended to receive higher L-dopa dosage and endure longer duration of L-dopa 
treatment. L-Dopa dosage as 281 mg/day and 4.2 mg/kg/day by ROC, as well as 269 
mg/day and 3.2 mg/kg/day by DTC were cut-off values for wearing-off. L-Dopa 
dosage and duration of L-dopa treatment were related to increased wearing-off 
development. Cumulative L-dopa dosage and L-dopa daily dosage were better 
predictive of wearing-off. Inadequate evidence was present for delayed L-dopa 
initiation. L-Dopa daily dosage no more than 275 mg or 4.2 mg/kg was regarded as 
safe.