Dyskinesia is the most common motor complication in advanced Parkinson’s disease (PD) and has a severe impact on daily life. But the mechanism of dyskinesia is still poorly understood. This study aims to explore risk factors for disabling dyskinesia in PD and further analyze the Vesicular Monoamine Transporter 2 (VMAT2) distribution (labeled with 18F-AV133) in the corpus striatum and the 18F-fluorodeoxyglucose (18F-FDG) metabolism of different brain regions by PET-CT. This is a cross-sectional study involving 135 PD patients. They were divided into disabling dyskinesia group (DD group, N=22) and non-dyskinesia group (ND group, N=113). All the patients were agreed to undergo PET-CT scans. Clinical data were analyzed between two groups by using multivariate logistic regression analysis, and risk factors for disabling dyskinesia were then determined. The standard uptake value ratios (SUVr) of 18F-AV133 in the corpus striatum and the 18F-FDG metabolism of different brain regions were identified and calculated by the software. 16.3% patients have disabling dyskinesia. DD group were more likely to have longer disease duration, higher Hoehn-Yahr degree, more severe clinic symptoms, more frequent sleep behavior disorder, and higher levodopa dose equivalency than ND group (P<0.05). After adjusting confounding factors by multivariate logistic regression, DD group had longer PD duration and high levodopa dose equivalency compared with ND group (P<0.05). There is no significant difference between the VMAT2 distribution (labeled with 18F- AV133) in the putamen and caudate between two groups. And the 18F-FDG metabolic changes in cortical and subcortical regions did not show a significant difference between the two groups either (P>0.05). Long PD duration and high levodopa dose equivalency were two independent risk factors for disabling dyskinesia in PD patients. Compared to non-dyskinesia PD patients, there was no significant dopamine decline of the nigrostriatal system in disabling dyskinesia PD patients. Activities of different brain regions were not different between the two groups by 18F-FDG PETCT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.