Objective: To explore the effect of scanning signal intensity on the peripapillary vessel density measured by optical coherence tomography angiography (OCTA). Methods: This study was a single-center cross-sectional study. All the participants received comprehensive examinations including height, weight, blood pressure,intraocular pressure, axial length, and OCTA scan of the optic disc. The effect of OCTA scanning signal intensity on the peripapillary vessel density was analyzed using the generalized estimation equation. Results: A total of 186 participants with 359 eyes were included in this study. The mean age of all the participants was (47.86±17.86)years old, and the average peripapillary vessel density was (17.75±1.99)mm?1. In a univariate analysis,peripapillary vessel density was associated with the axial length (β=?0.5120, P<0.001) and the scanning signal intensity (β=1.0240, P<0.001). After adjusting for age, gender, axial length, and optic disc area in the multivariate analysis, the OCTA scanning signal intensity was still significantly associated with the peripapillary vessel density (β=0.9721, P<0.001). Conclusion: The peripapillary vessel density is significantly negatively associated with the axial length and optic disc area, significantly positively associated with the scanning signal intensity. In clinical practice, the influence needs to be considered.