BACKGROUND Medication adherence is essential to optimizing blood pressure (BP) control. Prior research has demonstrated differences in pharmacy refill patterns according to antihypertensive drug class. No prior study has assessed the association between drug class and day-to-day adherence. METHODS Between 2011 and 2014, we enrolled a convenience sample of 149 patients with persistently uncontrolled hypertension from two inner-city clinics and concurrently measured adherence of up to four antihypertensive medications using electronic pillboxes during the interval between two primary care visits. The main outcome was mean percent of days adherent to each drug. Mixed effects regression analyses were used to assess the association between drug class and adherence adjusting for age, gender, race, ethnicity, education, health insurance, coronary artery disease, heart failure, chronic kidney disease, diabetes, number of medications, days monitored, and dosing frequency. RESULTS The mean age was 64 years; 72% women, 75% Hispanic, 88% prescribed ≥ 1 BP medication. In unadjusted analyses, adherence was lower for beta-blockers (70.9%) compared to angiotensin receptor blocking agents (75.0%, P = 0.11), diuretics (75.9%, P < 0.001), calcium channel blockers (77.6%, P < 0.001) and angiotensin-converting enzyme inhibitors (78.0%, P < 0.0001). In the adjusted analysis, only dosing frequency (P = 0.0001) but not drug class (P = 0.71) was associated with medication adherence. CONCLUSIONS Antihypertensive drug class was not associated with electronically measured adherence after accounting for dosing frequency amongst patients with uncontrolled hypertension. Low adherence to beta-blockers may have been due to the common practice of prescribing multiple daily dosing. Providers may consider using once daily formulations to optimize adherence and should assess adherence among all treated patients with uncontrolled hypertension.