The aim of this hypothesis was to examine the association of retinal vessel tortuosity with diabetes and diabetic retinopathy (DR).A clinic-based study of 327 participants (224 with diabetes and 103 non-diabetic controls) aged ≥ 18 years. DR was graded from fundus photographs according to the modified Airlie House Classification system and categorised into mild non-proliferative DR (NPDR), moderate NPDR and vision-threatening DR (VTDR). Retinal vessel tortuosity was measured from disc-centred retinal photographs. Measurements were taken, using a semi-automated computer program by a single grader, of arterioles and venules within 0.5 to 2 disc diameters away from the optic disc.There were 114 (44%) participants with DR. In the multivariate analysis, retinal arteriolar and venular tortuosity were increased in participants with diabetes without DR (mean difference 12.4 × 10(-5) and 13.3 × 10(-5), respectively; both p < 0.05) and in those with DR (mean difference 15.4 × 10(-5) and 15.0 × 10(-5), respectively; both p < 0.01) compared with non-diabetic participants. Among participants with diabetes, increased arteriolar tortuosity was significantly associated with mild NPDR (OR 1.53, 95% CI 1.03-2.05, per SD increase in arteriolar tortuosity) and moderate NPDR (OR 1.67, 95% CI 1.10-2.55) but not VTDR (OR 0.91, 95% CI 0.54-1.54). No association with DR was found for venular tortuosity.Persons with diabetes had more tortuous retinal vasculature than persons without diabetes. In persons with diabetes, increased arteriolar tortuosity was associated with mild and moderate stages of DR. This suggests that retinal vascular tortuosity might be an early indicator of microvascular damage in diabetes; thus, further investigation is indicated.