This meta-analysis compares health care resource use costs, adherence, and persistence between groups of patients taking antihypertensives as single-pill combinations (SPCs) vs free-equivalent components (FEC) based on a structured review of published studies. The search yielded 12 retrospective database studies included in analyses. The mean difference in combined total annual all-cause and hypertension-related health care costs was $1357 (95% confidence interval [CI], $778–$1935) lower in favor of SPC than FEC groups. Adherence, measured as the mean difference in medication possession ratio, was estimated to be 8% higher for patients naive to prior antihypertensives and 14% higher for nonnaive SPC patients compared with corresponding FEC patients. Persistence in the SPC groups was twice as likely as the FEC groups (pooled risk ratio, 2.1; 95% CI, 1.1–4.1). Improved adherence and persistence may have contributed to the lower costs in the SPC groups via improved clinical outcomes.