OBJECTIVES: To investigate the prevalence and potential determinants of cost-related non-adherence (CRNA) in US adults with heart failure (HF). DESIGN: A serial cross-sectional analysis using nationally representative data from 2012 to 2021 of the US Medical Expenditure Panel Survey. SETTING: Population-based. PARTICIPANTS: Adult participants with HF diagnosis. OUTCOME MEASURES: Self-report of never getting or delaying getting prescription medicine because of costs. RESULTS: We included 1753 patients with HF (mean age 69.36 [95% CI, 68.23 to 70.48]) years, 47.85% men and 17.09% non-Hispanic Black. The overall weighted prevalence of CRNA was 7.94% (6.40-9.81), increasing from 3.09% (1.29-7.24) in 2012 to 13.69% (8.99-20.32) in 2018 and decreasing to 8.71% (3.82-18.67) in 2021. The prevalence of CRNA was higher among patients <
65 years than those ≥65 years (11.78% vs 6.04%), and was more prevalent among patients with lower family income, with no insurance or public insurance, and with a greater comorbidity burden. The highest prevalence of CRNA was found among uninsured patients (18.54 [8.01-37.30]). Among patients <
65 years, patients with CRNA had significantly lower utilisation of sodium glucose cotransporter-2 inhibitors and slightly lower use of beta blockers and ACEi/ARBs. The out-of-pocket cost for medication was higher among those with CRNA, especially cost on central nervous system medicines. CONCLUSIONS: CRNA was prevalent among patients with HF, disproportionately affecting those younger than 65 years, with lower socioeconomic status, and higher comorbidity burden. Interventions are needed to reduce financial burden and enhance medication adherence.