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Abstract Adherence to antihypertensives is crucial for control of blood pressure. This study analyzed factors and interventions that could affect adherence to antihypertensives in the US. PubMed, Scopus, Web of Science, and Embase were searched on January 21, 2022 and December 25, 2023 for studies on the adherence to antihypertensives in the US. Nineteen studies and 23 545 747 patients were included in the analysis, which showed that adherence to antihypertensives was the highest among Whites (OR: 1.47, 95% CI 1.34–1.61 compared to African Americans). Employment status and sex were associated with insignificant differences in adherence rates. In contrast, marital status yielded a significant difference where unmarried patients demonstrated low adherence rates compared to married ones (OR: 0.8, 95% CI 0.67–0.95). On analysis of comorbidities, diabetic patients reported lower adherence to antihypertensives (OR: 0.95, 95% CI 0.92–0.97); furthermore, patients who did not have Alzheimer showed higher adherence rates. Different BMIs did not significantly affect the adherence rates. Patients without insurance reported significantly lower adherence rates than insured patients (OR: 3.93, 95% CI 3.43–4.51). Polypill users had higher adherence rates compared with the free‐dose combination (OR: 1.21, 95% CI 1.2–1.21), while telepharmacy did not prove to be as effective. Lower adherence rates were seen among African Americans, uninsured, or younger patients. Accordingly, interventions such as fixed‐dose combinations should be targeted at susceptible groups. Obesity and overweight did not affect the adherence to antihypertensives.