BackgroundFixed-dose combination (FDC) antihypertensive therapy is recommended by hypertension guidelines to improve adherence and blood pressure control. However, its association with healthcare utilization and health-related quality of life (HRQoL) among patients with apparent treatment-resistant hypertension (aTRH) remains unexplored. This study evaluated the association of FDC versus multi-pill combination (MPC) antihypertensive therapy with healthcare utilization and HRQoL among United States (US) adults with medication-defined aTRH.MethodsWe conducted a pooled cross-sectional study using data from the Medical Expenditure Panel Survey (2013–2022). Medication-defined aTRH was defined as adults aged ≥18 years with a hypertension diagnosis who were prescribed ≥4 antihypertensive medications from different classes. Medication-defined aTRH patients were then categorized as FDC users if they were prescribed at least one FDC antihypertensive product and as MPC users if they were prescribed antihypertensive classes as separate pills. Healthcare utilization outcomes included office-based visits, outpatient department visits, prescription fill, emergency department visits, home health visits, and inpatient night. HRQoL outcomes included Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Inverse probability of treatment weighting (IPTW) was performed to balance covariates. IPTW negative binomial and linear regression models were used to assess the associations between FDC antihypertensive therapy versus MPC antihypertensive therapy and healthcare utilization and HRQoL, respectively.ResultsThe study included 3,131 adults with medication-defined aTRH, of whom 1,518 were FDC users and 1,613 were MPC users. In IPTW models, FDC use was associated with lower rates of office-based visits (rate ratio [RR] = 0.760; 95% confidence interval [CI]: 0.683–0.846), prescription fills (RR = 0.854; 95% CI: 0.791–0.921), emergency department visits (RR = 0.667; 95% CI: 0.551–0.807), and inpatient nights (RR = 0.596; 95% CI: 0.403–0.879). FDC use was also associated with a higher PCS score; IPTW model (β = 2.686; 95% CI: 1.589–3.783). No significant association was observed with MCS score.ConclusionAmong US adults with medication-defined aTRH, FDC antihypertensive therapy was associated with lower healthcare utilization and better physical HRQoL compared with MPC therapy. These findings suggest that an FDC-containing regimen may represent a valuable treatment-simplification strategy in patients requiring multiple antihypertensive classes.