<jats:sec id="sec001"> <jats:title>Introduction</jats:title> <jats:p>Good adherence of antihypertensives is recommended for the accomplishment of hypertension therapy. The number of medications and characteristics contributing to medication regimen complexity, such as dosage forms and dosing frequency, are known to influence medication adherence. However, the effect of medication regimen complexity on the therapeutic efficacy of medicines remains to be clarified. In the present study, we retrospectively investigated the effect of number of medications and medication regimen complexity on medication adherence and therapeutic efficacy in patients with hypertension.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>According to the inclusion and exclusion criteria, 1,057 patients, who were on medications including antihypertensives on admission at the Mie University Hospital between July 2018 and December 2018, were enrolled in this study. Poor blood pressure management was defined if the systolic or diastolic blood pressure were ≥140 mmHg or ≥ 90 mmHg. Medication regimen complexity was quantified using the medication regimen complexity index (MRCI) score.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>Among 1,057 patients, 164 and 893 patients were categorized into poor and good adherence groups, respectively. The multivariate analyses revealed that age ≥ 71 years and oral MRCI score ≥ 19.5 but not number of oral medications were extracted as risk factors for poor medication adherence. Medication adherence and blood pressure management were poor in the group with oral MRCI score ≥ 19.5, regardless of the age. The rate of readmission was similar.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusion</jats:title> <jats:p>Our study is the first to demonstrate that medication regimen complexity rather than number of medications is closely related to medication adherence and blood pressure management. Hence, physicians and/or pharmacists should consider the complexity of medication regimens while modifying them.</jats:p> </jats:sec>