Introduction In the US, cardiovascular diseases (CVD) are the leading cause of death and disability. Cost-related non-adherence (CRMN) can have serious consequences and worsen CVD outcomes. We examined the relationship between CVD risk factors and CRMN among US adults. Methods CDC?s 2019-2021 National Health Interview Survey (NHIS) data was used to examine CRMN among adults, categorized into three groups based on reported risk factors. We used chi-square tests, logistic regression to determine factors associated with CRMN. Results Among 49,464 participants, young, unmarried individuals, females, less educated, and participants from South had higher CRMN than older, married individuals, males, and those with higher education residing in the other regions. Current smokers and those with more CVD risk factors also had a higher CRMN than former smokers and never-smokers. Conversely, those aged 65 or older, with high-income, and excellent self-rated health had lower CRMN than younger participants, low-income families, and those with poor self-health. Public insurance and Medicaid participants had lower CRMN than uninsured (OR 0.13, 95% CI, 0.04-0.45, and OR 0.24, 95% CI, 0.15-0.36). Stratified regression analysis by disease status, i.e., diabetes, hypertension, and hyperlipidemia, revealed participants with high-income had lower odds of CRMN (OR 0.38, 95% CI 0.28-0.50; OR 0.39, 95% CI, 0.28-0.58; OR 0.37, 95% CI 0.27-0.51 respectively) than those with lower incomes. Conclusion Adults under 65 with more CVD risk factors are at higher risk of CRMN. Hence, robust prescription drug coverage and targeted interventions are necessary to lower CRMN in those with CVD risk factors.