INTRODUCTION: Globally, diabetic retinopathy (DR) is a major cause of blindness. Sub-Saharan Africa is projected to see the largest proportionate increase in the number of people living with diabetes over the next two decades. Screening for DR is recommended to prevent sight loss; however, in many low and middle-income countries, because of a lack of specialist eye care staff, current screening services for DR are not optimal. The use of artificial intelligence (AI) for DR screening, which automates the grading of retinal photographs and provides a point-of-screening result, offers an innovative potential solution to improve DR screening in Tanzania. METHODS AND ANALYSIS: We will test the hypothesis that AI-supported DR screening increases the proportion of persons with true referable DR who attend the central ophthalmology clinic following referral after screening in a single-masked, parallel group, individually randomised controlled trial. Participants (2364) will be randomised (1:1 ratio) to either AI-supported or the standard of care DR screening pathway. Participants allocated to the AI-supported screening pathway will receive their result followed by point-of-screening counselling immediately after retinal image capture. Participants in the standard of care arm will receive their result and counselling by phone once the retinal images have been graded in the usual way (typically after 2-4 weeks). The primary outcome is the proportion of persons with true referable DR attending the central ophthalmology clinic within 8 weeks of screening. Secondary outcomes, by trial arm, include the proportion of persons attending the central ophthalmology clinic out of all those referred, sensitivity and specificity, number of false positive referrals, acceptability and fidelity of AI-supported screening. ETHICS AND DISSEMINATION: The London School of Hygiene & Tropical Medicine, Kilimanjaro Christian Medical Centre and Tanzanian National Institute of Medical Research ethics committees have approved the trial. The results will be submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ISRCTN18317152.