To assess the effect of prior cardiovascular interventions on long-term clinical outcomes in patients with symptomatic atherothrombosis, the risk factor profiles, treatment patterns, and 24-month outcomes of patients in the United States with and without prior cardiovascular intervention (catheter-based, surgical, or lower-limb amputation) enrolled in the global REACH (REduction of Atherothrombosis for Continued Health) Registry were compared. Of the 17,521 US outpatients aged > or =45 years with established coronary artery disease, cerebrovascular disease, or peripheral artery disease enrolled in the REACH Registry between December 1, 2003 and June 1, 2004 who had > or =1 follow-up visit, 11,925 (68.1%) had a previous cardiovascular intervention. Prior intervention was most common in patients with coronary artery disease (76.7%) and least common in patients with cerebrovascular disease (14.6%) at baseline. Patients with prior cardiovascular intervention were significantly more likely to be taking antihypertensive, antithrombotic, or lipid-lowering therapies than those without prior intervention (P < 0.0001 for each therapy). However, 24-month Kaplan-Meier event rates for the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were similar between patients with and without prior intervention (9.10% vs. 9.00%; P = 0.49). Thus, in the US REACH Registry, prior cardiovascular intervention was not associated with an increased risk of subsequent cardiovascular ischemic events during follow-up. Patients without prior cardiovascular intervention had a lower intensity of risk factor modification at baseline and appear to represent an at-risk, undertreated population.