BACKGROUNDCardiovascular disease (CVD) prevention in diabetes requires broad-based treatment of dyslipidemia, hypertension, and hyperglycemia. The independent contribution of all combinations of risk factor control to CVD risk has not been evaluated.OBJECTIVETo estimate the independent association of control of glycosylated hemoglobin (A1C), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with risk of cardiovascular disease hospitalization.DESIGNNon-concurrent longitudinal cohort study.PATIENTSThe study included 26,636 patients with type 2 diabetes who were members of an integrated group model HMO with multiple A1C, SBP, and LDL-C measurements.MAIN MEASURESPatients were followed for a mean (SD) of 5.6 (2.5) years until they died or disenrolled, or until 31 December 2010. The outcome was a first-observed CVD hospitalization. Using the mean of all A1C, SBP, and LDL-C measures during follow-up, we created dichotomous categories of A1C control (< 7 %), SBP control (< 130 mmHg), and LDL-C control (< 100 mg/dL) to estimate the incidence rate of CVD hospitalization associated with all combinations of risk factor control adjusting for demographic and clinical characteristics.KEY RESULTSPatients with no controlled risk factors (18.2/1,000 person-years, 95 % CI 16.5−20.2) or with only A1C in control (16.9, 15.0−19.0) had the highest rate of CVD hospitalization, whereas those with all three risk factors controlled (7.2, 6.2−8.4) or with SBP and LDL-C in control (6.1, 5.1−7.2) had the lowest rates. Those with only SBP or LDL-C in control, A1C and SBP controlled, or A1C and LDL-C controlled had statistically similar incidence between the highest and lowest rates.CONCLUSIONSMaintaining SBP < 130 mmHg or LDL-C < 100 mg/dL was significantly associated with reduced CVD hospitalization risk, especially when both risk factors were well controlled. Maintaining A1C < 7 % was not independently associated with reduced CVD hospitalization risk.Electronic supplementary materialThe online version of this article (doi:10.1007/s11606-012-2320-1) contains supplementary material, which is available to authorized users.