There is an independent progressive epidemiologic relation between glycemia and cardiovascular disease (CVD) events; however, whether lowering glucose levels with currently available therapies can reduce CVD events remains unknown. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is designed to answer this question in high-risk patients with type 2 diabetes mellitus. In ACCORD, 10,251 patients with type 2 diabetes and other CVD risk factors or CVD were randomly allocated to intensive glycemic control, targeting a glycosylated hemoglobin (HbA1c) level <6%, or standard glycemic control, targeting an HbA1c level of 7.0%-7.9%. All participants are provided with diabetes education, glucose-monitoring equipment, and antidiabetic medications. All participants in the intensive glycemic control group are started on > or = 2 classes of agents. Doses are intensified or a new medication class is added every month if HbA1c levels are > or = 6% or if >50% of premeal or postmeal capillary glucose readings are >5.6 mmol/L (100 mg/dL) or >7.8 mmol/L (140 mg/dL), respectively. All drug combinations are permitted, and drugs are reduced only because of side effects or contraindications. Annual training, menus of approaches for intensification, regular electronic messaging, audits of achieved glycemia, and central feedback to sites support glycemic intensification strategies in intensive participants. In participants in the standard glycemic control group, therapy is intensified whenever HbA1c is > or = 8%, and antihyperglycemic drugs that promote hypoglycemia (ie, insulin or insulin secretagogues) are reduced if HbA1c persistently decreases to <7% in the setting of hypoglycemia. ACCORD addresses the hypothesis that aggressive glucose lowering prevents CVD events in patients with type 2 diabetes. It is focused on the levels of glycemia achieved using a variety of strategies, not on the specific therapies used. It will also provide information on how to safely approach near-normal levels of glucose control in clinical practice and evidence to support future clinical guidelines for diabetes management in older adults.