Objective Given the increasing burden of repetitive intravitreal injections in diabetic macular oedema (DMO) treatment, non-invasive markers of treatment outcome are needed. Hence, we aimed to examine retinal oximetry parameters as markers of need for intravitreal aflibercept in patients with DMO. Methods This study was based on data from a 12-month clinical trial including 35 eyes of 25 patients with centre involving DMO. Retinal oximetry, visual acuity (VA) and central retinal thickness (CRT) were performed at baseline (BL). Patients then received 3 monthly injections of aflibercept followed by focal/grid laser photocoagulation. From month 4 (M4) through 12 (M12), patients were followed monthly and additional injections were given pro re nata if criteria of retreatment were met. We evaluated the difference in need for intravitreal aflibercept in groups of eyes with the highest and lowest retinal arteriolar and venular oxygen saturations, respectively. Results From BL-M12, overall VA letter score improved by 8.7 (7.2-10.2). Likewise CRT reduced by 100.7 (68.2-133.3) μm and the mean number of injections was 4.3 (3.8-4.8). Overall retinal arteriolar and venular oxygen saturations were 95.7 (93.0-98.4)% and 62.7 (59.4-65.9)% at BL. Eyes with the highest retinal arteriolar oxygen saturations had significantly more injections between BL and M12 compared with eyes with the lowest retinal arteriolar oxygen saturations (5.0 (4.2-5.8) vs 3.6 (3.1-4.0), p=0.002). Conclusion Higher retinal arteriolar oxygen saturation independently predicted the need for more intravitreal aflibercept during the first year of DMO treatment and may serve as a valuable adjunctive to established procedures for retinal imaging in terms of individualised treatment plans. Trial registration number NCT02554747.