Cardiovascular disease (CVD) is a systemic process involving multiple vascular beds and includes coronary heart disease (CHD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). All these manifestations are associated with an increased risk of subsequent myocardial infarction, stroke, and death. Guideline-directed medical therapy is recommended for all patients with CVD. In a cohort of US veterans, we identified 1,242,015 patients with CVD receiving care in 130 Veterans Affairs facilities from October 1, 2013 to September 30, 2014. CVD included diagnoses of CHD, PAD, or ICVD. We assessed the frequency of risk factor optimization and the use of guideline-directed medical therapy in patients with CHD, PAD alone, ICVD alone, and PAD + ICVD groups. A composite of 4 measures (blood pressure <140/90 mm Hg, A1c <7% in diabetics, statin use, and antiplatelet use in eligible patients), termed optimal medical therapy (OMT) was compared among groups. Multivariate logistic regression was performed with CHD as the referent category. CHD comprised 989,380 (79.7%), PAD alone 70,404 (5.7%), ICVD alone 163,730 (13.2%), and PAD + ICVD 18,501 (1.5%) of the cohort. Overall, only 36% received OMT with adjusted odds ratios of 0.54 (95% CI 0.53 to 0.55), 0.77 (0.76 to 0.78), and 0.97 (0.94 to 1.00) for patients with PAD alone, ICVD alone, and PAD + ICVD, respectively, compared with patients with CHD. In conclusion, OMT was low in all groups. Patients with PAD alone and ICVD alone were less likely to receive OMT than those with CHD and PAD + ICVD.