BACKGROUND: Retinal microvascular signs may provide insights into the structure and function of small vessels that are associated with renal disease. We examined the relationship of retinal microvascular signs with both prevalent and incident end-stage renal disease (ESRD) in a multi-ethnic Asian population. METHODS: A total of 5763 subjects (aged ≥ 40 years) from two prospective population-based studies (the Singapore Malay Eye Study and the Singapore Prospective Study) were included for the current analysis. Retinopathy was graded using the modified Airlie House classification system. Retinal vascular parameters were measured using computer-assisted programs to quantify the retinal vessel widths (arteriolar and venular caliber) and retinal vascular network (fractal dimension). Data on ESRD was obtained by record linkage with the ESRD cases registered by National Registry of Diseases Office, Singapore. Multi-variable adjusted regression analyses were performed to assess the associations of baseline retinal vascular parameters and prevalent and incident ESRD. RESULTS: At baseline, 21(0.36%) persons had prevalent ESRD. During a median follow-up of 4.3 years, 33 (0.57%) subjects developed ESRD. In our analyses, retinopathy was associated with prevalent ESRD (multi-variable adjusted odds ratio [OR], 3.21, 95% confidence interval [CI]: 1.28-8.05) and incident ESRD (multi-variable adjusted hazard ratio [HR], 2.51, 95%CI: 1.14-5.54). This association was largely seen in person with diabetes (HR, 2.60, 95%CI: 1.01-6.66) and not present in persons without diabetes (HR, 1.65, 95%CI: 0.14-18.98). Retinal arteriolar caliber, retinal venular caliber and retinal vascular fractal dimension were not associated with ESRD. CONCLUSION: Retinopathy signs in persons with diabetes are related to an increased risk of ESRD; however, other microvascular changes in the retina are not associated with ESRD.