PURPOSE/AIM: To investigate the association between retinal vascular tortuosity and traditional- and vascular-related risk factors in persons with diabetes. METHODS: We recruited 224 diabetic patients. Retinal vascular tortuosity was measured from fundus photographs. Association of tortuosity with the following factors was assessed after adjusting for significant co-factors: diabetes duration, HbA1c, systolic blood pressure (SBP), cholesterol and body mass index (BMI), flicker-light induced retinal vasodilatation, and markers of endothelial function and inflammation (skin microvacular responses to acetylcholine iontophoresis, soluble e-selectin, inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelin-1, total nitrite, C-reactive protein). RESULTS: Adjusting for age and gender, longer diabetes duration was associated with more tortuous retinal arterioles (mean difference in arteriolar tortuosity 5.85 × 10(-5), 95% Confidence Interval 1.44-10.3 × 10(-5); p = 0.016; ≤10 versus >10 years duration). Reduced flicker-light induced retinal vasodilatation was associated with tortuous arterioles and venules (mean difference in arteriolar tortuosity 5.62 × 10(-5), 4.50-6.72 × 10(-5); p < 0.001 and in venules 5.94 × 10(-5), 3.33-8.55 × 10(-5); p < 0.001; comparing highest versus lowest tertile of flicker-light vasodilatation). These associations remained after adjusting for co-factors. Diabetes duration explained about 36% and flicker-light vasodilatation 25% of the variation in retinal arteriolar tortuosity. No associations were found between retinal arteriolar or venular tortuosity and HBA1c, SBP, cholesterol, BMI and serum markers of endothelial function. CONCLUSIONS: Increased retinal arteriolar tortuosity was related to longer diabetes duration and reduced flicker-light induced vasodilatory response, suggesting that retinal vascular tortuosity in adults with diabetes may be influenced by multiple diabetes-related physio-pathological changes.