AIM: We evaluated the associations of heart rate variability (HRV) with incident vision-threatening retinopathy and retinopathy progression among adults with type 2 diabetes. METHODS: Participants recruited to the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study with HRV measures at baseline were analysed. HRV measures included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Low SDNN was defined as SDNN <8.2 ms; low rMSSD as rMSSD <8.0 ms. We used multivariable adjusted Cox proportional hazards and modified Poisson regression models to generate risk estimates for incident vision-threatening retinopathy and retinopathy progression, respectively. RESULTS: A total of 5810 participants without incident vision-threatening retinopathy at baseline (mean age 62 years, 40.5% women, 63.5% White) were included. Over a median of 4.7 years, 280 incident vision-threatening retinopathy cases requiring treatment occurred. Low HRV (vs. normal HRV) was associated with higher risk of incident vision-threatening retinopathy (adjusted hazard ratio 1.32 [95%CI 1.03-1.71] and 1.14 [95%CI 1.01-1.28] for low SDNN and rMSSD, respectively). In the subset of 2184 participants with complete eye examinations at baseline and 4 years, 191 experienced retinopathy progression, and low HRV (vs. normal HRV) was associated with a higher risk of retinopathy progression (adjusted relative risks 1.36 [95%CI 1.01-1.83] and 1.36 [95%CI 1.01-1.84] for low SDNN and rMSSD, respectively). CONCLUSIONS: Cardiac autonomic neuropathy, as assessed by low HRV, was independently associated with increased risks of incident vision-threatening retinopathy and overall retinopathy progression in a large cohort of adults with type 2 diabetes.