Less than one third of patients with hypertension achieve optimal blood pressure control. Poor medication adherence has been identified as one contributor to uncontrolled blood pressure.This study was conducted to test the hypothesis that patients who require an increase in their antihypertensive regimen have poorer adherence with medication compared with patients who remain on a stable regimen.Health plan enrollment and pharmacy claims data were used to perform a prospective cohort study and a nested case-control study in patients newly starting antihypertensive therapy. In the prospective cohort study, cumulative medication adherence (CMA, the percentage of days the patient had pills available, calculated as the total number of days of medication dispensed, excluding the final prescription, divided by the total number of days between the first and last antihypertensive prescriptions in the observation period) was compared between patients who required an increase in therapy and patients who remained on a stable antihypertensive regimen. In the nested case-control analysis, interval medication adherence (IMA, the ratio of the number of days of medication dispensed in a single prescription divided by the number of days until the next prescription is filled) during the prescription interval immediately before an increase in the antihypertensive regimen was compared with a similar interval in control patients without an increase matched by age, medication, number of days of medication dispensed, and months since initiation of therapy.The study included data from 5089 patients (mean [SD] age, 47.8 [13.0] years; 50.0% women). Over a median (interquartile range) of 23 (9–49) months of initial antihypertensive treatment, 935 patients (18.4%) had an increase in regimen. After adjusting for age, duration of treatment, number of prescribing physicians, and specific medication, patients with a regimen increase had a 12.0% higher CMA compared with patients remaining on a stable regimen (P < 0.001). IMA for the period immediately before the increase was not significantly different in patients with an increase compared with matched controls (98.3% vs 101.0%, respectively).Among these insured patients newly starting antihypertensive therapy, patients who required an increase in therapy had similar or slightly better medication adherence compared with patients remaining on a stable regimen. Poor adherence was not predictive of intensification of the antihypertensive regimen.