OBJECTIVE: We investigated whether cardiovascular autonomic dysfunction was associated with glycemic control status over time in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: From 1999 to 2000, cardiovascular autonomic nerve function testing (AFT) was performed on patients with type 2 diabetes (n = 1,021) and was followed-up in 2006 and February 2008. Tests for cardiovascular autonomic functions measured heart rate variability parameters (expiration-to-inspiration [E/I] ratio, responses to the Valsalva maneuver, and standing). AFT scores were determined from the results of the each test as follows: 0 for normal and 1 for abnormal. We began with those who had a score of 0 and assessed the changes in total score along with biannual A1C levels. RESULTS: At follow-up, the development of cardiovascular autonomic dysfunction was 34.5% (E/I ratio 21.9%, Valsalva maneuver 77.8%, and posture 58.9%; n = 783). The development of cardiovascular autonomic dysfunction was higher in older patients (P < 0.001); in those with longer duration of diabetes (P < 0.001); of hypertension (P = 0.005), and of diabetic retinopathy (P < 0.001); and in those who had higher levels of microalbuminuria (P = 0.002). Logistic regression analysis revealed that the development of cardiovascular autonomic dysfunction was strongly associated with the mean A1C level during the follow-up period (mean A1C >9.0% vs. <or=7.0%, odds ratio 2.984, 95% CI 1.177-7.561; P = 0.021). CONCLUSIONS: The development of cardiovascular autonomic dysfunction was independently associated with microvascular complications and glycemic control status during this 7.5-year follow-up in patients with type 2 diabetes.