<p class="abstract"><strong>Background:</strong> Diabetic retinopathy is the most common cause of visual loss affecting the economically productive age group globally. Diabetic macular oedema (DMO) results from leakage of fluid into the retinal interstitial space. Anti-vascular endothelial growth factor (anti-VEGF) drugs are the first line treatment for DMO. Since monthly injections are required, this treatment regimen can prove very costly. Of the anti-VEGF drugs, bevacizumab is the most cost-effective. The pro re nata (PRN) method is the current standard of care. However, the treat and extend (T and E) regimen can potentially decrease the patient burden on hospitals. Thus far, no randomised clinical trials have been performed using Bevacizumab in a treat and extend versus pro re nata regimen.</p><p class="abstract"><strong>Methods:</strong> A prospective randomised non-inferiority clinical trial testing bevacizumab (1.25 mg) in a treat and extend method versus the pro re nata method is being conducted. Patients will be randomised using a simple computer-based randomised algorithm. The primary outcome is non-inferiority within a five-letter margin for the T and E regimen versus the PRN regimen.</p><p class="abstract"><strong>Conclusions: </strong>This study aims to inform a key area in the literature on the treatment of DMO, i.e. whether a T and E regimen is non-inferior to a PRN regimen in the treatment of DMO with bevacizumab, which is the only anti VEGF available in resource poor settings. It is motivated by the cost involved in the treatment of DMO as well as the treatment burden on both the patient and the health institution at which the patient is receiving treatment.</p><p class="abstract"><strong>Trial registration:</strong> The trial has been registered on the Pan-African clinical trials registry (PACTR202001624880-753).</p>