Background: TCS are at increased risk of CVD, but few clinical studies have comprehensively evaluated CVD risk factors through physical exams, lipid panels, and health behaviors in North American patients. Methods: Eligible TCS were < 50 y at diagnosis and treated with only first line CHEM. TCS underwent physical exams, had fasting lipid panels, and completed questionnaires regarding co-morbidities and health behaviors. Age, race, and educational status-matched controls (1:1) were chosen from the general population using the 2011-2012 National Health and Nutrition Examination Survey. Odds ratios (OR) of outcomes among TCS versus matched controls were estimated using logistic regression models. Results: We evaluated 680 consecutively enrolled TCS. Median age at diagnosis was 31 y (range, 15-49) and at clinical evaluation 38 y (range, 19-68). Median time since CHEM was 4.3 y (range, 1-30). Compared to normative controls, TCS were more likely to be overweight (OR = 1.65; 95% CI 1.26-2.16), have total cholesterol ≥ 240 mg/dL (OR = 2.19; 95% CI 1.12-4.28) and LDL ≥ 160 mg/dL (OR = 3.05; 95% CI 1.03-9.00), and report alcohol use > 2 days/week (OR = 2.13; 95% CI 1.64-2.77). In contrast, they were more likely to have a waist circumference < 40 inches (OR = 1.32; 95% CI 1.04-1.66); engage in vigorous (OR = 2.64; 95% CI 2.11-3.29) or moderate (OR = 1.62; 95% CI 1.30-2.03) physical activity, and not smoke (OR = 2.95; 95% CI 2.14-4.08). TCS were about 3 times more likely overall to report excellent, very good, or good health compared to controls (P < 0.05). No significant differences were found comparing HDL, triglycerides, or self-reported hypertension (P > 0.05). Conclusions: Although North American TCS appear more likely to exercise and abstain from smoking compared to normative controls, a greater proportion are overweight and have higher fasting total cholesterol and LDL levels. Health care providers should screen TCS for CVD risk factors, and encourage practices consistent with a healthy lifestyle. Future research should elucidate mechanisms of increased CVD risk and ultimately develop customized prevention and intervention strategies.