In the Diabetes Control and Complications Trial (DCCT), 1441 insulin-dependent diabetic patients in the primary prevention and secondary intervention cohorts were randomly assigned to either conventional or intensive therapy and followed for up to 9 years. Baseline and biennial measurements of autonomic function (R-R variation, Valsalva ratio, and postural testing) as well as quarterly assessment of autonomic symptoms were performed throughout the trial. There were no differences at baseline between patients randomized to intensive vs conventional therapy. In general, autonomic abnormalities increased during the trial; however, R-R variation was less abnormal in the intensively treated secondary intervention (7% with abnormal results at 4-6 years) compared with the conventionally treated group (14% with abnormal results, p = 0.004) and in the combined cohorts (5% of intensive treatment subjects with abnormal results vs 9% of conventional treatment subjects, p = 0.0017). There were few abnormal Valsalva ratios or postural tests at baseline or during the trial. No significant difference in Valsalva ratio or postural tests occurred between the intensive and conventional treatment groups. Both the R-R variation and the Valsalva ratio had significantly greater slopes of decline over time in the patients randomized to conventional therapy (1.48 points per year and 0.015 per year, respectively) compared to those randomized to intensive therapy (0.912 points per year and 0.0025 per year). Of the symptoms related to autonomic function, only incomplete bladder emptying was significantly more common in the conventional group. In summary, the DCCT documented that intensive therapy can slow the progression and the development of abnormal autonomic tests.