AbstractTo determine the effect of hypertension (HTN) on the peripapillary microvasculature in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR). The patients were classified into three groups: the control group (group 1), T2DM group (group 2), and both T2DM and HTN group (group 3). Peripapillary vessel density (VD) was compared using analysis of covariance and linear regression analysis was performed to identify the factors affecting the peripapillary VD. A total of 286 eyes were enrolled: 124 in group 1, 111 in group 2, and 51 in group 3. The peripapillary VDs for the full area were 18.3 ± 0.6, 17.8 ± 1.0, and 17.3 ± 1.2 mm⁻¹ in group 1, group 2, and group 3, respectively, which were significantly different after adjustment for age and best-corrected visual acuity (P < 0.001). In post hoc analyses, group 1 versus group 2 (P < 0.001), group 1 versus group 3 (P < 0.001), and group 2 versus group 3 (P = 0.001) showed significant differences. In linear regression analysis, HTN (B = − 0.352, P = 0.043) and peripapillary retinal nerve fiber layer (pRNFL) thickness (B = 0.045, P < 0.001) were significantly associated with peripapillary VD in T2DM patients. Peripapillary VD in T2DM patients without clinical DR were lower compared to normal controls, and they were more decreased when HTN was comorbid. The combination of ischemic damage by high blood pressure and impairment of the neurovascular unit by hyperglycemia would result in more severe deterioration of peripapillary microvasculature, and this impairment could be also reflected by pRNFL thinning.