Cardiovascular disease, including myocardial infarction, heart failure, and stroke, is a leading cause of death in patients with diabetes. For this reason, the ultimate goal of diabetes management is to prevent and treat these serious complications. There is convincing evidence from epidemiological and pathophysiological studies that higher level of blood glucose and HbA1C are at great risk for cardiovascular disease. However, although the benefits of improved glycemic control for prevention of microvascular disease, such as diabetic nephropathy, retinopathy, and neuropathy, have been demonstrated in many large clinical trials, the results of trials assessing the preventive effects of glycemic control for cardiovascular disease are intriguing. In the UKPDS trial, no differences were observed for cardiovascular end-points and mortality. However, in the 10-year post-trial follow-up, intensive treatment group achieved a significant reduction in the incidence of myocardial infarction and all-cause mortality. On the contrary, intensive treatment group did not raise the cardiovascular benefits in the ACCORD trial, whereas all-cause mortality was 22% higher in this group. In fact, the comparisons of results of different trials are complex because of diversities in characteristics of participating subjects and in concomitant therapies. In this lecture, I will look back on these large clinical trials and discuss the importance of glucose control for prevention of cardiovascular disease in diabetic patients.