Background It is unclear if achieving multiple risk factor (RF) goals through protocol-guided intensive medical therapy is feasible or improves outcomes in type 2 diabetes (T2DM). Objectives We sought to quantify the relationship between achieved RF goals in the BARI 2D (Bypass Angioplasty Investigation Revascularization 2 Diabetes) trial and cardiovascular events/survival. Methods We performed a nonrandomized analysis of survival/cardiovascular events and control of 6 RFs (nonsmoker, non-HDL-C <130 mg/dl, triglycerides <150 mg/dl, blood pressure [systolic <130 mm Hg; diastolic <80 mm Hg], hemoglobin A1c <7%) in BARI 2D. Cox models with time-varying number of RFs in control were adjusted for baseline number of RFs in control, clinical characteristics, and trial randomization assignments. Results In 2,265 patients (mean age 62 years, 29% women) followed for 5 years, the mean ± SD number of RFs in control improved from 3.5 ± 1.4 out of 6 at baseline to 4.2 ± 1.3 at 5 years, p < 0.0001. The number of RFs in control during the trial was strongly related to death (global p = 0.0010) and the composite of death, myocardial infarction and stroke (global p = 0.0035) in fully adjusted models. Participants with 0 to 2 RFs in control during follow-up had a 2-fold higher risk of death (hazard ratio [HR]: 2.0; 95% CI: 1.3 to 3.3, p = 0.0031) and a 1.7-fold higher risk of the composite endpoint (HR: 1.7; 95% CI 1.2 to 2.5, p = 0.0043), compared with those with 6 RFs in-control. Conclusions Simultaneous control of multiple RFs through protocol-guided intensive medical therapy is feasible and relates to cardiovascular morbidity and mortality in patients with coronary disease and T2DM.