To determine whether the recommended screening interval for diabetic retinopathy (DR) in the UK can safely be extended beyond 1 year. Systematic review of clinical and cost-effectiveness studies. Nine databases were searched with no date restrictions. Randomised controlled trials (RCTs), cohort studies, prognostic or economic modelling studies which described the incidence and progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes mellitus of either sex and of any age reporting incidence and progression of DR in relation to screening interval (vs annual screening interval) and/or prognostic factors were included. Narrative synthesis was undertaken. 14 013 papers were identified, of which 11 observational studies, 5 risk stratification modelling studies and 9 economic studies were included. Data were available for 262 541 patients of whom at least 228 649 (87%) had type 2 diabetes. There were no RCTs. Studies concluded that there is little difference between clinical outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there was high loss to follow-up (13-31%), heterogeneity in definitions of low risk and variation in screening and grading protocols for prior retinopathy results. Observational and economic modelling studies in low-risk patients show little difference in clinical outcomes between 1-year and 2-year screening intervals. The lack of experimental research designs and heterogeneity in definition of low risk considerably limits the reliability and validity of this conclusion. Costeffectiveness findings were mixed. There is insufficient evidence to recommend a move to extend the screening interval beyond 1 year.