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Background: Despite numerous interventions targeting medication adherence in patients with uncontrolled hypertension, practice-based trials in Latino patients are scant., Objective: To evaluate the effect of a systems-level adherence intervention, delivered by medical assistants (MAs), versus a comparison condition on medication adherence and blood pressure (BP) in 119 hypertensive Latino patients who were initially non-adherent to their antihypertensive medications., Study Design: Randomized control trial., Participants: Patients (50% women; mean age, 61 years) were recruited from April 2013 to August 2015 in a community-based practice in New York., Intervention: Systems-level approach that included an office system component built into the electronic health record and a provider support component consisting of nine MA-delivered health coaching sessions for improving medication adherence. The comparison group received the standard health coaching procedures followed at the clinic., Main Outcome Measures: The primary outcome was rate of medication adherence measured by an electronic monitoring device (EMD) across 6 months. The secondary outcomes were self-reported medication adherence measured by the eight-item Morisky Medication Adherence Scale (MMAS-8) and BP reduction from baseline to 6 months., Key Results: Adherence as measure by EMD worsened for both groups (p = 0.04) with no between-group difference (- 9.6% intervention and - 6.6% control, p = 0.66). While systolic BP improved in both groups, the difference between groups was not significant (- 6 mmHg in intervention vs. - 2.7 mmHg in control, p = 0.34). In contrast, the intervention group had a greater improvement in self-reported adherence (mean change 1.98 vs. 1.26, p = 0.03) when measured using the MMAS-8., Conclusions: Among Latinos with poorly controlled BP who were non-adherent to their antihypertensive medications, a systems-level intervention did not improve adherence as measured by EMD nor blood pressure. However, many patients reported challenges to using the EMD. Improvements in self-reported adherence suggest that this measure captures different aspects of adherence behavior than EMD., Clinical Trial Registration: NCT03560596.