The 2017 American Heart Association Scientific Statement on meditation and cardiovascular risk suggested that meditation may be considered as an adjunct to guideline-directed cardiovascular risk-reduction interventions. Meditation could potentially increase physical and mental relaxation, leading to improved outcomes after a major cardiovascular event. We hypothesized that meditation is associated with lower cardiovascular risk in the US general population. Using data from the 2012 and 2017 National Health Interview Survey, we identified all patients with hypercholesterolemia, systemic hypertension (SH), diabetes mellitus (DM), stroke, and coronary artery disease (CAD), as well as those who reported that they meditate. Multivariable logistic regression analyses were performed to evaluate the association between meditation and risk of hypercholesterolemia, SH, DM, stroke, and CAD, adjusting for potential confounders. Of 61,267 the National Health Interview Survey participants, 5,851 (9.6%) participated in some form of meditation. After adjusting for age, gender, body mass index, race, marital status, cigarette smoking, sleeping duration, and depression, meditation was independently associated with a lower prevalence of hypercholesterolemia (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.54 to 0.79; p = 0.001), SH (OR 0.86; 95% CI 0.75 to 0.99; p = 0.04), diabetes (OR 0.70; 95% CI 0.59 to 0.84; p = 0.0001), stroke (OR 0.76; 95% CI 0.58 to 0.99; p = 0.04), or CAD (OR 0.51; 95% CI 0.39 to 0.66; p <0.001), compared with those who did not meditate. In conclusion, using a large national database, we found that meditation is associated with a lower prevalence of cardiovascular risks factors and disease.