ObjectiveTo systematically review the medication adherence of patients with hypertension treated with single-pill combinations (SPC) compared with free combination therapy (FEC). MethodsThe PubMed, Embase, Cochrane Library, Web of Science, CBM, WanFang Data, and CNKI databases were electronically searched to collect cohort studies and randomized controlled trials (RCTs) related to the objectives from inception to March 2025. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using R 4.3.3 software. ResultsA total of 21 studies were included, comprising 4 RCTs and 17 cohort studies, involving 461 030 patients. Meta-analysis showed that SPC therapy significantly improved medication adherence compared with FEC in terms of proportion of days covered (PDC) (OR=2.53, 95%CI 1.67 to 3.82, P<0.01) and medication possession ratio (MPR) (OR=2.05, 95%CI 1.23 to 3.42, P=0.02), with statistically significant differences. However, there was no statistically significant difference in blood pressure reduction between SPC and FEC for both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P>0.05). ConclusionCurrent evidence shows that SPC can improve medication adherence in patients with hypertension. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.