OBJECTIVE - Optimal glycemic control slows diabetic retinopathy (DR) development and progression and is the standard of care for type 1 diabetes. However, these glycemic goals are difficult to achieve and sustain in clinical practice. The Renin Angiotensin System Study (RASS) showed that renin-angiotensin system (RAS) blockade can slow DR progression. In the current study, we evaluate whether glycemic control influenced the benefit of RAS blockade on DR progression in type 1 diabetic patients. RESEARCH DESIGN AND METHODS - We used RASS data to analyze the relationships between two-steps or more DR progression and baseline glycemic levels in 223 normotensive, normoalbuminuric type 1 diabetic patients randomized to receive 5 years of enalapril or losartan compared with placebo. RESULTS - A total of 147 of 223 patients (65.9%) had DR at baseline (47 of 74 patients [63.5%] in placebo and 100 of 149 patients [67.1%] in the combined treatment groups [P = 0.67]). Patients with two-steps or more DR progression had higher baseline A1C than those without progression (9.4 vs. 8.2%, P < 0.001). There was no beneficial effect of RAS blockade (P = 0.92) in patients with baseline A1C ≤ 7.5%. In contrast, 30 of 112 (27%) patients on the active treatment arms with A1C > 7.5% had two-steps or more DR progression compared with 26 of 56 patients (46%) in the placebo group (P = 0.03). CONCLUSIONS - RAS blockade reduces DR progression in normotensive, normoalbuminuric type 1 diabetic patients with A1C > 7.5%.Whether this therapy could benefit patients with A1C ≤7.5% will require long-term studies of much larger cohorts.