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To compare changes in retinal vascular calibre after 2 years of treatment with intravitreal bevacizumab (BVZ) or dexamethasone implant (DEX) in patients with centre-involving diabetic macular oedema (DMO).At baseline, 88 eyes of 61 patients with DMO were recruited in a prospective, multicentre, randomised, single-masked clinical trial. Of these subjects, 22 BVZ-treated (52%) and 22 DEX-treated (48%) eyes of 34 patients (56%) had gradable retinal photographs at both the baseline and 24-month visits. Retinal vascular calibre was measured from digital fundus photographs and summarised as central retinal artery (CRAE) and vein (CRVE) equivalents in all gradable eyes at baseline and 24 months.At 24 months, 40.9% of BVZ and 45.5% of DEX eyes gained 10 or more letters (p=0.77). There was concurrent reduction in mean central macular thickness, −157.7 μm in BVZ and −192.5 μm in DEX-treated eyes (p=0.40). DEX-treated eyes showed a statistically significant reduction in CRVE compared with BVZ-treated eyes, with a mean change from baseline of −31.78 to +4.34 µm, respectively (p<0.001). CRAE showed a non-statistically significant trend towards reduction over time in DEX-treated eyes compared with BVZ-treated eyes, with a mean change from baseline of −6.09 and +1.66, respectively (p=0.077).DEX had a significant narrowing effect on venular diameter in eyes with DMO not seen with BVZ. The changes in retinal vascular calibre suggest that these agents have a differing actions effects retinal vasculature and thereby suggest a potentially different mechanism of action on reducing DMO.NCT01298076.